Rotational spun material covered medical appliances and methods of manufacture

ABSTRACT

A medical appliance or prosthesis may comprise one or more layers of rotational spun nanofibers, including rotational spun polymers. The rotational spun material may comprise layers including layers of polytetrafluoroethylene (PTFE). Rotational spun nanofiber mats of certain porosities may permit tissue ingrowth into or attachment to the prosthesis. Additionally, one or more cuffs may be configured to allow tissue ingrowth to anchor the prosthesis.

RELATED APPLICATIONS

This application claims priority to the following applications: U.S.Provisional Application No. 61/587,088 filed on Jan. 16, 2012 titledForce Spun Fibers and Medical Appliances; U.S. Provisional ApplicationNo. 61/637,693 filed on Apr. 24, 2012 titled Rotational Spun MaterialCoated Medical Appliances and Method of Manufacture; and U.S.Provisional Application No. 61/672,633 filed on Jul. 17, 2012 titledRotational Spun Material Coated Medical Appliances and Method ofManufacture. Each of these three applications is hereby incorporated byreference in its entirety.

TECHNICAL FIELD

The present disclosure relates generally to medical devices. Morespecifically, the present disclosure relates to medical appliances orother prostheses, particularly those made of, constructed from, coveredor coated with rotational spun materials including polymers such aspolytetrafluoroethylene (PTFE).

BRIEF DESCRIPTION OF THE DRAWINGS

The patent or application file contains at least one drawing executed incolor. Copies of this patent or patent application publication withcolor drawings will be provided by the Office upon request and paymentof the necessary fee.

The embodiments disclosed herein will become more fully apparent fromthe following description and appended claims, taken in conjunction withthe accompanying drawings. These drawings depict only typicalembodiments, which will be described with additional specificity anddetail through use of the accompanying drawings in which:

FIG. 1A is a perspective view of a rotational spinning apparatus.

FIG. 1B is a top view of the rotational spinning apparatus of FIG. 1A.

FIG. 2A is a perspective view of another embodiment of a rotationalspinning apparatus.

FIG. 2B is a top view of the rotational spinning apparatus of FIG. 2A.

FIG. 3A is a perspective view of a covered stent.

FIG. 3B is a cross sectional view of the covered stent of FIG. 3A takenthrough line 3B-3B.

FIG. 4A is a perspective view of a rotational spun covering on amandrel.

FIG. 4B is a perspective view of the covering of FIG. 4A partiallyremoved from the mandrel.

FIG. 4C is a perspective view of the covering of FIG. 4A repositioned onthe mandrel.

FIG. 4D is a perspective view of a scaffolding structure wound aroundthe covering and mandrel of FIG. 4C.

FIG. 4E is a perspective view of the scaffolding structure of FIG. 4Dwith a second rotational spun covering.

FIG. 5 is a perspective view of a covered stent including cuffs.

FIG. 6 is a front view of a medical appliance frame structure.

FIG. 7A is a detail view of a portion of the frame of FIG. 6.

FIG. 7B is a detail view of an end of the frame of FIG. 6.

FIG. 7C is an alternate configuration of a portion of the frame of FIG.6.

FIG. 8 is an end view of a frame having flared ends.

FIG. 9 is front view of a frame having flared ends.

FIG. 10 is a front view of a wire being shaped to form a frame.

FIG. 11A is a scanning electron micrograph (SEM at 170×) of a rotationalspun material created from a PTFE dispersion combined with polyethyleneoxide (PEO) and water.

FIG. 11B is an SEM (at 950×) of the material of FIG. 11A.

FIG. 12A is an SEM (at 170×) of a rotational spun material having mediumfiber diameters which were collected on a sheet.

FIG. 12B is an SEM (at 950×) of the material of FIG. 12A.

FIG. 13A is an SEM (at 170×) of a rotational spun material having mediumfiber diameters which were collected on a rotating mandrel.

FIG. 13B is an SEM (at 950×) of the material of FIG. 13A.

FIG. 14A is an SEM (at 170×) of a rotational spun material having largerfibers which were collected on a rotating mandrel.

FIG. 14B is an SEM (at 950×) of the material of FIG. 14A.

FIG. 15 is an SEM (at 950×) of a rotational spun material having largerfibers which were collected on a sheet.

FIG. 16A is an SEM (at 170×) of a rotational spun material having mediumfibers which were collected on a sheet.

FIG. 16B is an SEM (at 950×) of the material of FIG. 16A.

FIG. 17A is an SEM (at 170×) of a rotational spun material havingsmaller fibers which were collected on a sheet.

FIG. 17B is an SEM (at 950×) of the material of FIG. 17A.

FIG. 18A is an SEM (at 170×) of a rotational spun material collected ona horizontally mounted mandrel.

FIG. 18B is an SEM (at 950×) of the material of FIG. 18A.

FIG. 19 is a cross sectional view (at 370×) of an exemplary construct ofmultiple layers of rotational spun materials.

FIG. 20 is an SEM (at 950×) of a construct comprising a rotational spunPTFE material and an FEP layer.

FIG. 21A is an SEM (at 170×) of a rotational spun material spun at 4500RPM.

FIG. 21B is an SEM (at 170×) of a rotational spun material spun at 5000RPM.

FIG. 21C is an SEM (at 170×) of a rotational spun material spun at 5500RPM.

FIG. 21D is an SEM (at 170×) of a rotational spun material spun at 6000RPM.

FIG. 21E is an SEM (at 170×) of a rotational spun material spun at 7000RPM.

FIG. 22A is an SEM (at 170×) of a rotational spun material spun from a0.08 g/ml PEO/PTFE mixture.

FIG. 22B is an SEM (at 170×) of a rotational spun material spun from a0.09 g/ml PEO/PTFE mixture.

FIG. 22C is an SEM (at 170×) of a rotational spun material spun from a0.10 g/ml PEO/PTFE mixture.

FIG. 22D is an SEM (at 170×) of a rotational spun material spun from a0.11 g/ml PEO/PTFE mixture.

FIG. 23A is a cross-sectional view of two body lumens with a stentdisposed therein.

FIG. 23B is a side view of a portion of a stent comprising a taperedsegment.

FIG. 23C is a side view of another embodiment of a stent comprising atapered segment.

FIG. 24 is an immunonistochemistry light microscopy color image of aportion of an explanted material sample and a digitally marked up copyof the same image.

FIG. 25 is a color image of a trichrome-stained histology lightmicroscopy image for a portion of one explanted material sample.

FIG. 26 is color image of a trichrome-stained histology light microscopyimage for a portion of an explanted material sample having multiplelayers.

DETAILED DESCRIPTION

Medical appliances may be deployed in various body lumens for a varietyof purposes. Stents may be deployed, for example, in the central venoussystem for a variety of therapeutic purposes including the treatment ofocclusions within the lumens of that system. The current disclosure maybe applicable to stents or other medical appliances designed for thecentral venous (“CV”) system, peripheral vascular (“PV”) stents,abdominal aortic aneurism (“AAA”) stents, bronchial stents, esophagealstents, biliary stents, coronary stents, gastrointestinal stents, neurostents, thoracic aortic endographs, or any other stent or stent graft.Further, the present disclosure may be equally applicable to otherprosthesis such as grafts. Any medical appliance comprised of materialsherein described may be configured for use or implantation withinvarious areas of the body, including vascular, cranial, thoracic,pulmonary, esophageal, abdominal, or ocular application. Examples ofmedical appliances within the scope of this disclosure include, but arenot limited to, stents, vascular grafts, stent grafts, cardiovascularpatches, reconstructive tissue patches, hernia patches, general surgicalpatches, heart valves, sutures, dental reconstructive tissues, medicaldevice coverings and coatings, gastrointestinal devices, blood filters,artificial organs, ocular implants, and pulmonary devices, includingpulmonary stents. For convenience, many of the specific examplesincluded below reference stents. Notwithstanding any of the particularmedical appliances referenced in the examples or disclosure below, thedisclosure and examples may apply analogously to any prostheses or othermedical appliance.

As used herein, the term stent refers to a medical appliance configuredfor use within a bodily structure, such as within a body lumen. A stentmay comprise a scaffolding or support structure, such as a frame, and/ora covering. Thus, as used herein, “stent” refers to both covered anduncovered scaffolding structures.

It will be readily understood that the components of the embodiments asgenerally described and illustrated in the Figures herein could bearranged and designed in a wide variety of different configurations.Thus, the following more detailed description of various embodiments, asrepresented in the Figures, is not intended to limit the scope of thedisclosure, but is merely representative of various embodiments. Whilethe various aspects of the embodiments are presented in drawings, thedrawings are not necessarily drawn to scale unless specificallyindicated.

The phrases “connected to,” “coupled to,” and “in communication with”refer to any form of interaction between two or more entities, includingmechanical, electrical, magnetic, electromagnetic, fluid, and thermalinteraction. Two components may be coupled to each other even thoughthey are not in direct contact with each other. For example, twocomponents may be coupled to each other through an intermediatecomponent.

The directional terms “proximal” and “distal” are used herein to referto opposite locations on a stent or another medical appliance. Theproximal end of an appliance is defined as the end closest to thepractitioner when the appliance is disposed within a deployment devicewhich is being used by the practitioner. The distal end is the endopposite the proximal end, along the longitudinal direction of theappliance, or the end furthest from the practitioner. It is understoodthat, as used in the art, these terms may have different meanings oncethe appliance is deployed (i.e., the “proximal” end may refer to the endclosest to the head or heart of the patient depending on application).For consistency, as used herein, the ends labeled “proximal” and“distal” prior to deployment remain the same regardless of whether theappliance is deployed. The longitudinal direction of a stent is thedirection along the axis of a generally tubular stent. In embodimentswhere a stent or another appliance is composed of a metal wire structurecoupled to one or more layers of a film or sheet like components, suchas a polymer layer, the metal structure is referred to as the“scaffolding” or “frame,” and the polymer layer as the “covering” or“coating.” The terms “covering” or “coating” may refer to a single layerof polymer, multiple layers of the same polymer, or layers comprisingdistinct polymers used in combination. Furthermore, as used herein, theterms “covering” and “coating” refer only to a layer or layers which arecoupled to a portion of the scaffold; neither term requires that theentire scaffold be “covered” or “coated.” In other words, medicalappliances wherein portion of the scaffold may be covered and a portionremain bare, are within the scope of this disclosure. Finally, anydisclosure recited in connection with coverings or coatings mayanalogously be applied to medical devices comprising one or more“covering” layers with no associated frame or other structure. Forexample, a hernia patch comprising any of the materials described hereinas “coatings” or “coverings” is within the scope of this disclosureregardless of whether the patch further comprising a frame or otherstructure.

Medical device coverings may comprise multilayered constructs, comprisedof two or more layers which may be serially applied. Further,multilayered constructs may comprise nonhomogeneous layers, meaningadjacent layers have differing properties. Thus, as used herein, eachlayer of a multilayered construct may comprise a distinct layer, eitherdue to the distinct application of the layers or due to differingproperties between layers.

Additionally, as used herein, “tissue ingrowth” or “cellularpenetration” refer to any presence or penetration of a biological orbodily material into a component of a medical appliance. For example,the presence of body tissues (e.g. collagen, cells, and so on) within aopening or pore of a layer or component of a medical appliance comprisestissue ingrowth into that component. Further, as used herein,“attachment” of tissue to a component of a medical appliance refers toany bonding or adherence of a tissue to the appliance, includingindirect bonds. For example, tissue of some kind (e.g. collagen) maybecome attached to a stent covering (including attachment via tissueingrowth) and another layer of biologic material (such as endothelialcells) may, in turn, adhere to the first tissue. In such instances, thesecond biologic material (endothelial cells in the example), and thetissue (collagen in the example) are “attached” to the stent covering.

Furthermore, through the present disclosure, certain fibrous materials(such as rotational spun materials) may be referred to as inhibiting orpromoting certain biological responses. These relative terms areintended to reference the characteristics of the fibrous materials withrespect to non-fibrous materials or coatings. Examples of non-fibrouscoatings include non-fibrous PTFE sheets, other similarly formedpolymers, and the like. Examples of fibrous coatings include rotationalspun PTFE, electrospun PTFE, expanded PTFE, and other similarly formedpolymers or materials. Examples of spun fibrous coatings includerotational spun PTFE, electrospun PTFE, and other similarly formedpolymers or materials, and exclude expanded PTFE.

Lumens within the circulatory system are generally lined with a singlelayer (monolayer) of endothelial cells. This lining of endothelial cellsmakes up the endothelium. The endothelium acts as an interface betweenblood flowing through the lumens of the circulatory system and the innerwalls of the lumens. The endothelium, among other functions, reduces orprevents turbulent blood flow within the lumen. The endothelium plays arole in many aspects of vascular biology, including atherosclerosis,creating a selective barrier around the lumen, blood clotting,inflammation, angiogenesis, vasoconstriction, and vasodilation.

A therapeutic medical appliance which includes a covering of porous orsemi-porous material may permit the formation of an endothelial layeronto the porous surface of the blood contact side of the medical device.Formation of an endothelial layer on a surface, or endothelialization,may increase the biocompatibility of an implanted device. For example, astent which permits the formation of the endothelium on the insidediameter (blood contacting surface) of the stent may further promotehealing at the therapeutic region and/or have longer term viability. Forexample, a stent coated with endothelial cells may be more consistentwith the surrounding body lumens, thereby resulting in less turbulentblood flow or a decreased risk of thrombosis, or the formation of bloodclots. A stent which permits the formation of an endothelial layer onthe inside surface of the stent may therefore be particularlybiocompatible, resulting in less trauma at the point of application,fewer side effects, and/or longer term device viability. Medicalappliances including a covering of porous or semi-porous material may beconfigured to inhibit or reduce inflammatory responses by the bodytoward the tissue contacting side of the medical appliance, for example.Mechanisms such as an inflammatory response by the body toward themedical appliance may stimulate, aggravate, or encourage negativeoutcomes, such as neointimal hyperplasia. For example, a deviceconfigured to permit tissue ingrowth and/or the growth or attachment ofendothelial cells onto the blood contacting side of the device mayreduce the likelihood of negative flow characteristics and bloodclotting. Similarly, a device so configured may mitigate the body'sinflammatory response toward the material on, for example, the tissue ornon-blood contacting side of the device. By modulating the evokedinflammatory response, negative outcomes such as the presence ofbioactive inflammatory macrophages and foreign body giant cells may bereduced. This may aid in minimizing the chemical chain of responses thatmay encourage fibrous capsule formation surrounding the device andevents stimulating neointimal hyperplasia.

Rotational spun materials, such as those described herein, may be usedto comprise portions of medical appliances, such as stents, patches,grafts, and so forth. The present disclosure is applicable to anyimplantable medical appliance, notwithstanding any specific examplesincluded below. In other words, though particular medical appliances,such as stents or patches, may be referenced in the disclosure andexamples below, the disclosure is also analogously applicable to othermedical appliances, such as those which comprise a covering or layer ofpolymeric material.

In some embodiments, rotational spun nanofibers (and/or microfibers) maybe configured to permit interaction with nano-scale (and/or micro-scale)body structures, such as endothelial cells. Rotational spinning refersgenerally to processes involving the expulsion of flowable material fromone or more orifices, the material forming fibers which are subsequentlydeposited on a collector. Examples of flowable materials includedispersions, solutions, suspensions, liquids, molten or semi-moltenmaterial, and other fluid or semi-fluid materials. In some embodiments,the rotational spinning processes are completed in the absence of anelectric field.

For example, one embodiment of a rotational spinning process comprisesloading a polymer solution or dispersion into a cup or spinneretconfigured with orifices on the outside circumference of the spinneret.The spinneret is then rotated, causing (through a combination ofcentrifugal and hydrostatic forces, for example) the flowable materialto be expelled from the orifices. The material may then form a “jet” or“stream” extending from the orifice, with drag forces tending to causethe stream of material to elongate into a small diameter fiber. Thefibers may then be deposited on a collection apparatus. Exemplarymethods and systems for rotational spinning can be found in U.S. PatentPublication No. US2009/0280325, titled “Methods and Apparatuses forMaking Superfine Fibers,” which is herein incorporated by reference inits entirety.

Rotational spinning may be configured to create mats, tubes, or otherstructures comprised of elongate fibers, including nanofibers (i.e.fibers which are smaller than one micron in diameter) or microfibers(i.e. fibers which are between one micron and one millimeter indiameter). In some instances the fibers may be randomly disposed, whilein other embodiments the alignment or orientation of the fibers may besomewhat controlled or follow a general trend or pattern. Regardless ofany pattern or degree of fiber alignment, as the fibers are deposited ona collector or on previously deposited fibers; the fibers are not woven,but rather serially deposited on the collector or other fibers. Becauserotational spinning may be configured to create a variety of structures,as used herein, the terms “mat” or “non-woven mat or material” isintended to be broadly construed as referring to any such rotationalspun structure, including tubes, spheres, and so on.

The present disclosure relates to medical appliances which may have, incertain embodiments, metal scaffolding covered with at least one layerof rotational spun material, such as rotational spunpolytetrafluoroethylene (PTFE). Additionally, the present disclosurerelates to medical appliances formed of rotational spun materials whichmay not have scaffolding structures or have scaffolding structures whichare not made of metal. It will be appreciated that, though particularstructures and coverings are described below, any feature of thescaffolding or covering described below may be combined with any otherdisclosed feature without departing from the scope of the currentdisclosure.

FIGS. 1A, 1B, 2A, and 2B schematically illustrate certain embodiments ofrotational spinning apparatuses. FIGS. 3A and 3B illustrate anembodiment of a covered medical appliance. FIGS. 4A-4E illustratecertain steps in a process of manufacturing a multi-layered construct ofrotational spun materials. FIG. 5 illustrates an embodiment of a medicalappliance which includes cuffs at each end of a stent. FIGS. 6-10illustrate aspects of frames configured for use in connection withmedical appliances. Finally, FIGS. 11A-19 are scanning electronmicrographs (SEMs) of exemplary rotational spun materials. Again,regardless of whether a medical appliance illustrated in any particularfigure is illustrated with a particular covering or coating, or withoutany covering or coating at all, any embodiment of a medical appliancemay be configured with any of the combinations of coverings or coatingsshown or described herein.

FIG. 1A illustrates a rotational spinning apparatus 101. This Figure, aswell as FIGS. 1B, 2A, and 2B, discussed below, are intended toschematically illustrate the operation of a rotational spinningapparatus, and not meant to limit the particular structure, shape, orarrangement of rotational spinning apparatus components within the scopeof this disclosure. The illustrated apparatus 101 comprises a spinneret110 disposed near the center of a generally circular collector 115. Inthe illustrated embodiment the collector 115 forms a ring around thespinneret 110. The spinneret 110 further comprises orifices 117 locatedaround the circumference of the spinneret 110 and a reservoir 118.

The apparatus 101 may be utilized to create a mat of rotational spunfibers deposited on the collector 115. In some embodiments, thecollector 115 may be configured such that structures such as rods,tubes, or spheres of rotational spun fibers are created.

In some embodiments, the apparatus 101 may be utilized to create a matof rotational spun fibers by first filling the reservoir 118 with aflowable material. In some instances polymer dispersions, includingaqueous dispersions or polymer solutions may be used. The spinneret 110may then be rotated such that the dispersion, or other flowablematerial, is forced out of the orifices 117 as illustrated by the arrowsin FIG. 1A. Molecules, including polymer chains, may tend to disentangleand/or align as the material is forced through the orifice.Additionally, in some embodiments the orifice 117 comprises a needle ornozzle that extends from the outside circumference of the spinneret 110.Still further, in some embodiments the orifice 117 may comprise acannula configured with a quick connection, such as a luer connection,allowing for rapid exchange of various cannula sizes.

As the dispersion is expelled from the reservoir 118, drag or otheraerodynamic forces acting on the stream or jet of material may cause thestream of dispersion to elongate and bend, forming a relatively smalldiameter fiber of material. In some instances drag may be a shear forcewith respect to the stream. Additionally, certain components of thedispersion, such as the dispersion medium or solvent, may partially orfully evaporate as the material is drawn into fibers. In embodimentsutilizing flowable materials which have no solvent, such as moltenmaterial, there may be no evaporation as the material is drawn intofibers.

The fibers eventually contact, and are deposited on, the collector 115.The combination of forces described above may interact as the fibers aredeposited, causing the fibers to be disposed in random patterns on thecollector 115. In some embodiments, air currents may be introduced (forexample through the use of fans) to partially control the deposition ofthe fibers on the collector 115.

In embodiments utilizing certain flowable materials, the fibers may thenbe removed from the collector 115 and sintered, or sintered thenremoved. For example, sintering may be applicable to PTFE fibers,including PTFE fibers spun from a dispersion. The sintering process mayset or bond the structure of the mat and remove any remaining water orother dispersion medium or solvent.

In some embodiments, the mat may be treated at a first temperature toremove solvents and a second temperature to sinter the mat. For example,a PTFE mat spun from an aqueous dispersion may be first treated at atemperature below the sintering temperature of PTFE in order to removeany remaining water. For example, the mat may be heated to about 200degrees C. to remove any remaining water in the mat. Further, othermaterials such as solvents or fiberizing agents may be evaporated orotherwise driven off at this stage. In some embodiments—as furtherdetailed below—a PTFE dispersion may be mixed with polyethylene oxide(PEO) prior to rotational spinning the mat. As also discussed in theexamples below, concentrations of PEO to 60 wt % PTFE dispersion fromabout 0.04 g/ml to about 0.12 g/ml, including from about 0.06 g/ml toabout 0.08 g/ml may be used in some embodiments. In some instances, veryhigh or very low concentrations of PEO may lead to shrinkage duringsintering or sputtering during rotational spinning of the material.

Treating the spun mat at temperatures such as 200 degrees C. may forceoff remaining PEO as well as water. In some embodiments the PTFE mat maythen be sintered at about 385 degrees C. In other embodiments, PTFEsintering may be completed at temperatures from about 360 degrees C. toabout 400 degrees C., and/or at temperatures in excess of thecrystalline melt point of the PTFE (about 342 degrees C.). In otherinstances the mat may only be heated to the sintering temperature,removing the remaining water and/or PEO while simultaneously sinteringthe PTFE. Additionally or alternatively, in some embodiments solvents orother materials may be removed by rinsing the mat.

Sintering may set the structure of the mat even if the temperature atwhich the material is sintered is not sufficient to cause cross linkingof the polymer chains. PTFE sintering may create solid, void free, PTFEfibers.

FIG. 1B is a top view of the rotational spinning apparatus 101 of FIG.1A, illustrating the spinneret 110, the collector 115, and the reservoir118. In the illustration of FIG. 1B potential arced paths of the streamsof material interacting with drag forces are illustrated by arrows anddotted lines. These lines are exemplary and not intended to show theprecise path of the fibers. In many embodiments, the fibers may loopcompletely around the spinneret 110 before contacting the collector 115,including embodiments where the fiber path encircles the spinneret 110more than one time before contacting the collector 115.

The distance between the spinneret 110 and the collector 115 may impactthe diameter of the fibers. In some embodiments, the longer the fibersare drawn out before contacting the collector 115, the smaller theresulting fiber diameters. Similarly, smaller distances may beconfigured to produce larger diameter fibers.

Processes such as the exemplary process described above may be utilizedto create structures comprised of small diameter fibers, includingnanofibers. The fiber mat may then be incorporated into a medicalappliance configured for implantation in the human body. Some suchstructures, including nanofiber structures, may be configured to permittissue ingrowth and/or endothelial growth or attachment on the mat. Forexample the mat may be configured with openings within the fibers orsimilar structures configured to permit interaction with tissue and/orcells. As further detailed below, the percent porosity of a fiber mat,the thickness of the mat, and the diameter of the fibers comprising themat may each be configured to create a fiber mat with desiredproperties, including mats that tend to permit or resist tissue ingrowthand/or endothelial growth or attachment.

A number of variables may be controlled to affect the properties of arotational spun mat. Some of these variables include: the rotationalspeed of the spinneret; the viscosity of the solution, dispersion, orother flowable material; the temperature of the spinneret; introducedair currents; the thickness of the mat; and so on. In the case of fibersspun from molten material, the melt flow index (MFI) of the material mayalso impact the nature of the spun mat. In some embodiments, materialswith an MFI of from about 1 g/10 min to about 5000 g/10 min, includingfrom about 200 g/10 min to about 1500 g/10 min and from about 10 g/10min to about 30 g/10 min, will tend to form fibers when spun.

In other embodiments a rotational spun mat may be configured to resisttissue ingrowth into or through the mat. In such embodiments, the matmay be configured with very small pores, or essentially no pores at all,thus preventing tissue ingrowth into or through the mat. Certain medicalappliances may be constructed partially of rotational spun materialsconfigured to permit tissue ingrowth and/or endothelial growth orattachment and partially of rotational spun materials configured toresist tissue ingrowth and/or attachment. Characteristics of therotational spun fiber mat, such as porosity and average pore size, maybe controlled during the rotational spinning process to create certainmats which permit tissue ingrowth and/or endothelial growth orattachment and other mats which resist or are impermeable to tissueingrowth and/or attachment.

In some embodiments, a PTFE dispersion may be used to rotational spin amat or another structure comprised of PTFE nanofibers. Furthermore, insome exemplary embodiments PEO may be added to the PTFE dispersion priorto rotational spinning the material. The PEO may be added as afiberizing agent, to aid in the formation of PTFE fibers within thedispersion or during the process of rotational spinning the material. Insome instances the PEO may more readily dissolve in the PTFE dispersionif the PEO is first mixed with water. In some examples this increasedsolubility may reduce the time needed to dissolve PEO in a PTFEdispersion from as long as multiple days to as little as 30 minutes.After the material is rotational spun onto a collector, the material maythen be sintered as further described below. In some instances thesintering process will tend to set or harden the structure of the PTFE.Furthermore, as described above, sintering may also eliminate the waterand PEO, resulting in a mat of substantially pure PTFE. Additionally, asalso described above, the mat may first be heat treated at a temperaturebelow the sintering temperature of the PTFE, in order to remove waterand/or PEO from the mat. In some embodiments this step may be completedat about 200 degrees C.

The water, PEO, and PTFE amounts may be controlled to optimize theviscosity, PEO/PTFE ratio, or other properties of the mixture. In someinstances adding water to the PEO before mixing with the PTFE dispersionmay aid in reducing the number of solid chunks in the mixture, lower thepreparation time for the mixtures, and reduce the time needed for thecombined mixture to solubilize.

A variety of materials may be rotational spun to form structures for usein medical appliances. Exemplary materials which may be rotational spunfor use in implantable appliances include PTFE, fluorinated ethylenepropylene (FEP), Dacron or Polyethylene terephthalate (PET),polyurethanes, polycarbonate polyurethanes, polypropylene, Pebax,polyethylene, biological polymers (such as collagen, fibrin, andelastin), and ceramics.

Furthermore, additives or active agents may be integrated with therotational spun materials, including instances where the additives aredirectly rotational spun with other materials. Such additives mayinclude radiopaque materials such as bismuth oxide, antimicrobial agentssuch as silver sulfadiazine, antiseptics such as chlorhexidine or silverand anticoagulants such as heparin. Organic additives or components mayinclude fibrin and/or collagen. In some embodiments, a layer of drugs orother additives may be added to a rotational spun appliance duringmanufacture. Additionally, some appliances may be constructed with acombination of synthetic components, organic components, and/or activeingredients including drugs, including embodiments wherein an applianceis comprised of alternating layers of these materials. Moreover, in someembodiments a medical appliance may consist of layers of rotational spunmaterials configured to control the release of a drug or another activelayer disposed between such layers. Active layers or ingredients such asdrugs or other active agents may be configured to reduce or otherwisemodify or influence the biological response of the body to theimplantation of the medical appliance.

Additionally, in some embodiments the material supplied to the reservoir118 may be continuously supplied (for example by a feed line), includingembodiments where the reservoir is pressurized or supplied by apressurized source. Further, in some embodiments the material may beheated near or above its melting point prior to rotational spinning,including embodiments wherein the material is melted and not dispersedin a solvent. Thus, in some embodiments, rotational spinning moltenmaterial does not include the use of solvents; therefore there is noneed to remove solvents from the mat at a later step in the process. Insome instances the material may be supplied to the reservoir as pelletswhich are heated and melted within the reservoir.

Still further, in some instances the collector 115 may have anelectrostatic charge. Additionally, in some embodiments rotational spunstructures may be combined with electrospun structures, includingembodiments where some layers of material are rotational spun and someelectrospun, but both deposited on the same substrate or construct.Electrospinning, and its use in connection with medical appliances, isdescribed in U.S. patent application Ser. No. 13/360,444, filed on Jan.27, 2012 and titled “Electrospun PTFE Coated Stent and Method of Use,”which is hereby incorporated by reference in its entirety.

Referring specifically to FIGS. 2A and 2B, another schematic embodimentof a rotational spinning apparatus 201 is illustrated. FIGS. 2A and 2Billustrate an apparatus analogous to that shown in FIGS. 1A and 1B. Itwill be appreciated by one of skill in the art having the benefit ofthis disclosure that analogous components of the two apparatuses may beinterchangeable and that disclosure provided in connection with eachembodiment may be applicable to the other and vice versa.

FIG. 2A is a perspective view of the rotational spinning apparatus 201while FIG. 2B is a top view of the same. The rotational spinningapparatus 201 includes a spinneret 210 comprising a reservoir 218 andorifices 217. As compared to the apparatus 101 of FIGS. 1A and 1B, inthe embodiment of FIGS. 2A and 2B the collector 115 is configured as aplurality of cylindrical mandrels 216. Thus in FIGS. 2A and 2B theplurality of mandrels 216 are collectively designated as a collector215, but individually designated by the numeral 216. The term“collector” as used in connection with FIGS. 1A-2B, and indicated bynumerals 115 and 215, is intended to broadly refer to any collectiondevice or apparatus without defining a particular size, shape, ororientation. For example, in some embodiments the collector may beconfigured as a ring, such as the collector 115 illustrated in FIGS. 1Aand 1B. In other embodiments the collector 215 may be a plurality ofcylinders as shown in FIGS. 2A and 2B. In still other embodiments, thecollector may comprise a rotating belt (not shown), configured tofacilitate rotational spinning of a continuous sheet of material.

Embodiments configured to form a continuous sheet of rotational spunmaterial may be configured to produce mats, including mats from aboutone meter to about 9 meters in width, such as mats of about 3 meters inwidth. Also mats from about one foot wide to about one meter wide (aswell as larger or smaller mats) may be formed. In some instances, asintering oven may be positioned such that as the mat moves away fromthe spinneret (on the belt) the mat enters the oven and is sintered. Thesintered mat may then be collected onto a spool. Further, in someembodiments, the entire spool may then be cut into smaller widths,forming strips of material. For example, strips from about 0.1 inch wideto about 2 inches wide may be formed. Such strips may be utilized forthe construction of tubular appliances by wrapping the strips around amandrel. The strips may overlap and/or may be wound such that the tubeformed does not have a distinct seam along the length of the tube. Insome instances, the mat may be wound in multiple layers around themandrel. Further, the mat formed may be relatively thin, or film-like.The thickness of the covering formed on the mandrel (and othercharacteristics such as porosity) may be controlled by the number oflayers of film wound onto the mandrel.

In some embodiments, rotational spun tubular medical devices, such asstents, may comprise one or multiple bifurcations or branches. Thus,medical devices which comprise a single lumen which splits or bifurcatesinto two or more lumens are within the scope of this disclosure.Likewise, medical appliances comprising a main lumen with one ormultiple branch lumens extending from the wall of the main lumen arewithin the scope of this disclosure. For example, a thoracicstent—configured for deployment within the aorta—may comprise a mainlumen configured to be disposed in the aorta and branch lumensconfigured to extend into side branch vessels originating at the aorta.Similarly, in some embodiments such stents may alternately be configuredwith access holes in the main lumen configured to allow access (possiblyfor additional stent placement) and flow from the main vessel to anybranch vessels extending there from.

In some embodiments, a bifurcated medical appliance may be manufacturedby first creating a bifurcated mandrel in which the bifurcated mandrelportions are removable from the portion of the mandrel coinciding withthe main lumen. The leg or branch portions of the mandrel may be splayed180 degrees apart with a common axis of rotation. Thus, in someembodiments, the entire mandrel may form a T-shape. The entire mandrelmay then be rotated about the axis of the leg portions and rotationalspun fibers collected on the leg portions of the mandrel. The mandrelmay then be oriented to rotate about the axis of the main lumen portionof the mandrel, and any unwanted fibers disposed while spinning on thebifurcated leg portions may be wiped off. The mandrel may then berotated about the axis of the main lumen portion and fibers collected onthe main lumen portion of the mandrel. The entire mandrel may then beplaced in an oven and sintered. The mandrel portions associated with thebifurcated legs may then be removed from the leg or branch portions ofthe appliance, and the single lumen mandrel portion subsequently removedfrom the spun appliance. The appliance may then be placed on or within aframe structure, such as a stent frame. A dip or film coating (such asof FEP or PTFE) may then be applied over the construct to create animpervious outside layer and/or to further bond the frame to the spunportion of the appliance.

In any of the exemplary embodiments or methods disclosed herein, ininstances where the nanofibers are formed of PTFE, the sinteringtemperature may be from about 360 degrees C. to about 400 degrees C.,including at temperatures of about 385 degrees C. or at temperaturesabove the crystalline melting temperature of the PTFE, or about 342degrees C. Similarly, for other materials, sintering may be done at orabove the crystalline melting temperature of other spun polymers. Again,either prior to or as part of the sintering process, heat treating maybe configured to remove PEO and/or water, in instances where the PTFE orother polymer was combined with such elements prior to spinning the mat.

In the embodiment of FIGS. 2A and 2B, the mandrels 216 may be disposedabout the spinneret 210 in a generally circular configuration. In someembodiments, the mandrels 216 may be stationary while in otherembodiments the mandrels 216 may be configured to rotate about theiraxes. In some such embodiments the mandrels 216 may each be driven bythe same belt, allowing each to maintain the same rotational speed. Inother embodiments some or all of the mandrels 216 may be independentlydriven.

In the illustrated embodiment, the mandrels 216 are disposed vertically,or such that the axis of each mandrel is substantially parallel to theaxis of rotation of the spinneret. In another exemplary embodiment, oneor more of the mandrels 216 may be disposed horizontally, or such thatthe axis of those mandrels is substantially orthogonal to the axis ofrotation of the spinneret. In some embodiments, the axis of the mandrel216 may be generally parallel to the axes of fibers being spun.Horizontally disposed mandrels 216 may be configured to produce matshaving generally less fiber alignment than vertical mandrels. Horizontalmandrels may further be configured to produce mats with relativelyuniform thickness around the mandrel.

In addition to horizontal mandrels, further embodiments may comprisemandrels disposed in any relative position with respect to the axis ofthe spinneret. Mandrels mounted in any disposition may be configured asstationary collection devices or configured to rotate. Additionally,combinations of mandrels in a variety of positions may be usedsimultaneously. Furthermore, in some embodiments one or more mandrels216 may be configured for use in connection with a vacuum system. Forexample, openings in the surface of the mandrel, such a micro-porousmandrels 216, may tend to draw fibers toward the mandrel in instanceswhere the interior of the mandrel 216 has lower pressure than theexterior of the mandrel 216.

In embodiments wherein the mandrels 216 rotate, the spinning motion ofeach mandrel 216 may tend to deposit the fibers around the entiresurface of the mandrel. Thus, as the fibers are deposited on eachmandrel 216, a seamless tube of nanofiber material may form on eachmandrel 216. The density of the fibers, the thickness of the mat, andother characteristics may be controlled by such variables as thedistance from the spinneret 210 to the mandrels 216, the rotationalspeed of the spinneret 210, the rotational speed of the mandrels 216,the orientation of the mandrels 216, the characteristics of the solutionbeing spun, and so forth. In some instances, mats of rotational spunmaterial formed on a spinning mandrel 216 may thus comprise a tubularmembrane having no seam and substantially isotropic properties. In someinstances the collection mandrel 216 may rotate at rates between about 1RPM and about 2000 RPM during the rotational spinning process, includingrates from about 1000 RPM to about 1500 RPM, including about 1500 RPM,or about 50 RPM to about 300 RPM, including about 150 RPM. In someinstances, the rotational speed of one or more collection mandrels maybe related to the rate at which the apparatus produces fibers. Forexample, in some embodiments, faster mandrel rotational speed may becorrelated with higher total fiber production rates for the apparatus.

Furthermore, controlling the rotational speed of the mandrels 216 mayinfluence both the density of the mat formed on the mandrels 216 and thegeneral alignment of fibers in the mat. For instance, in someembodiments utilizing vertical mandrels, the faster the mandrel 216 isspinning the more the fibers may tend to be deposited in-line with otherfibers. Further, the relative density of the fibers, for example, asmeasured by percent porosity, may be controlled in part by therotational speed of the mandrels 216. FIGS. 13A-14B, discussed below,are SEMs of exemplary mats rotational spun onto rotating mandrels.

As further detailed in connection with FIGS. 4A-4E, once the fibers arerotational spun onto the mandrels 216 the fibers may be sintered. Insome embodiments a scaffolding structure, such as a stent wire, may alsobe on the mandrel 216, and the nanofibers rotational spun directly ontothe mandrel 216 and scaffolding structure.

FIGS. 3A and 3B illustrate an exemplary medical appliance: a stent 302.The stent 302 comprises a scaffolding structure 320 and a coveringcomprising an inner layer 325, an outer layer 330, and a tie layer 335.In other embodiments, a stent covering may have more or fewer layersthan the illustrated embodiment, including embodiments with only onecovering layer. Again, disclosure recited herein with respect tospecific medical appliances, such as stents, may also be applicable toother medical appliances.

The cover of the stent 302 of FIG. 3A comprises a flat end 321 and ascalloped end 322. At the flat end 321 of the illustrated embodiment,the cover of the stent 302 is cut substantially perpendicular to thelongitudinal axis of the stent 302. At the scalloped end 322, the coverof the stent 302 comprises cut away, or scalloped, portions at the endof the stent 302. Scalloped ends may be configured to reduce infoldingof the stent cover at the ends. For example, in some instances, a stentmay have a larger diameter than a vessel in which it is deployed. Thus,the vessel may partially compress the stent radially. In some instancesthis radial compression may create folds or wrinkles in flat cut stentcovers. These folds may then impede blood flow or lead to clottingwithin the vessel. Scalloped ends may reduce the occurrence of infoldingat the end of a radially compressed stent. It is within the scope ofthis disclosure to use either type of end on any end of any stent.

Membranes composed of rotational spun mats may have a microstructurecomposed of many fibers crossing each other at various and randompoints. The rotational spinning process may control the thickness ofthis structure and thereby, the relative permeability of the mat. Asmore and more fibers are rotational spun onto a mat, the mat may bothincrease in thickness and decrease in permeability (due to successivelayers of strands occluding the pores and openings of layers below).Certain details of this microstructure are shown in FIGS. 11A-19, whichare discussed in more detail below.

Mats produced in connection with the present disclosure may be describedby three general parameters: percent porosity, mat thickness, and fiberdiameter. Each of these parameters may impact the nature of the mat,including the tendency of the mat to permit tissue ingrowth and/orendothelial attachment or the tendency of the mat to resist tissueingrowth or endothelial attachment. Each of these parameters may beoptimized with respect to each other to create a mat having particularcharacteristics.

Percent porosity refers to the percent of open space to closed space (orspace filled by fibers) in a fiber mat. Thus, the more open the mat is,the higher the percent porosity measurement. In some instances, percentporosity may be determined by first obtaining an image, such as an SEM,of a rotational spun material. The image may then be converted to a“binary image,” or an image showing only black and white portions, forexample. The binary image may then be analyzed and the percent porositydetermined by comparing the relative numbers of each type of binarypixel. For example, an image may be converted to a black and white imagewherein black portions represent gaps or holes in the rotational spunmat while white portions represent the fibers of the mat. Percentporosity may then be determined by dividing the number of black pixelsby the number of total pixels in the image. In some instances, a code orscript may be configured to make these analyses and calculations.

In some embodiments, percent porosities from about 30% to about 80% maybe configured to permit tissue ingrowth into the layer and/or permitendothelial growth or attachment on the layer, including mats of about40% to about 60%, mats of about 45% to about 50%, or mats of about 50%porosity. Less open layers may be configured to resist such ingrowthand/or attachment. Because the fibers comprising the mat are depositedin successive layers, the second parameter, mat thickness, may berelated to porosity. In other words, the thicker the mat, the morelayers of fibers, and the less porous the mat may be. In someembodiments, mats from about 20 micrometers to about 100 micrometers maybe configured for use in connection with the present disclosure,including mats from about 40 micrometers to about 80 micrometers.Finally, the third parameter, fiber diameter, may be a measurement ofthe average fiber diameter of a sample in some instances. In someembodiments fiber diameters from about 50 nanometers to about 3micrometers may be used in connection with the present disclosure.Notwithstanding these or other specific ranges included herein, it iswithin the scope of this disclosure to configure a mat with anycombination of values for the given parameters.

In some embodiments the “average pore size” of the mat may be used as analternate or additional measurement of the properties of the mat. Thecomplex and random microstructure of rotational spun mats presents achallenge to the direct measurement of the average pore size of the mat.Average pore size can be indirectly determined by measuring thepermeability of the mat to fluids using known testing techniques andinstruments. Once the permeability is determined, that measurement maybe used to determine an “effective” pore size of the rotational spunmat. As used herein, the “pore size” of a rotational spun mat refers tothe pore size of a membrane which corresponds to the permeability of therotational spun mat when measured using ASTM standard F316 for thepermeability measurement. This standard is described in ASTM publicationF316 “Standard Test Methods for Pore Size Characteristics of MembraneFilters by Bubble Point and Mean Flow Pore Test,” which is incorporatedherein by reference. In some instances this test can be used as aquality control after configuring a mat based on the three parameters(percent porosity, thickness, and fiber diameter) discussed above.

In some applications it may be desirable to create a medical appliancesuch as stent 302 with an outer layer 330 which is substantiallyimpermeable. Such a layer may decrease the incidence of lumen tissuesurrounding the stent growing into or attaching to the stent. This maybe desirable in applications where the stent is used to treat stenosisor other occlusions; an impermeable outer layer may prevent tissue fromgrowing into or through the material toward or into the lumen of thestent and reblocking or restricting the body lumen. In some embodimentsa substantially impermeable outer layer may be produced by usingrotational spun mats with a percent porosity from about 0% to about 50%,including about 25%; a thickness from about 20 micrometers to about 100micrometers, including from about 40 micrometers to about 80micrometers; and fiber diameters from about 50 nanometers to about 3micrometers.

Additionally, or alternatively, a substantially impermeable mat may havean average pore size of about 0 microns to about 1.5 microns. In otherembodiments, the impermeable layer may have an average pore size of lessthan about 0.5 micron. In yet other embodiments, the impermeable layermay have an average pore size of less than about 1 micron. In someembodiments, the impermeable layer may be a layer other than the outerlayer, such as a tie layer, an intermediate layer, or an inner layer.

In one example, a medical appliance such as stent 302 may be coveredwith a rotational spun PTFE inner layer 325 and a rotational spun PTFEouter layer 330. The outer layer 330 may be configured to besubstantially impermeable to tissue ingrowth and/or attachment. In otherembodiments the impermeability of the stent may be provided by a tielayer 335 disposed between the outer layer 330 and the inner layer 325.For example, a substantially impermeable layer may be formed of FEPwhich is applied, for example, as a film or dip coating betweenrotational spun layers of PTFE. Furthermore, FEP may be rotational spunwith a small average pore size to create a substantially impermeablelayer. In some embodiments both the outer layer 330 and the tie layer335 may be configured to be substantially impermeable.

Dip coatings may be applied by dipping a portion of a layer or constructin a polymer dispersion. For example, a PTFE layer may be dip coated ona construct by adding 20 ml of water to 50 ml of a 60 wt % PTFEdispersion to thin the dispersion. A fiber mat may then dipped in thesolution to coat the mat. The dip coat may then sintered at 385 degreesC. for 15 minutes. Other concentrations of PTFE dispersions for dipcoatings are also within the scope of this disclosure.

Further, an FEP layer may be dip coated on a construct by adding 20 mlof water to 50 ml of a 55 wt % dispersion to thin the dispersion. Afiber mat may then dipped in the solution to coat the mat. The dip coatmay then cooked, for example, at 325 degrees C. for 15 minutes. Otherconcentrations of FEP dispersions for dip coatings are also within thescope of this disclosure. Additionally, polymer dispersions may besprayed or otherwise applied onto a surface (such as a fiber mat) tocoat the surface. Such coatings may be heat treated after application.

In some embodiments, more or less water, for example from about 10 ml toabout 50 ml, may be added to similar amounts and concentrations of thedip dispersions above to thin the dispersions. Additionally, substancesother than, or in addition to, water may be used to thin a dispersionfor dip coating. For example, a surfactant or a solvent may be used. Insome such cases the surfactant or solvent may later be removed from theconstruct, including embodiments where it is allowed to evaporate whenthe coat is sintered or cooked. Alcohols, glycols, ethers, and so forthmay be so utilized.

In some embodiments it may be desirable to create a medical appliancesuch as stent 302 with an outer layer 330 which is more porous. A porousouter layer 330 may permit healing and the integration of the prosthesisinto the body. For instance, tissue of the surrounding lumen may growinto the porous outer diameter or attach to the outer diameter layer.This tissue ingrowth may permit, modulate, and/or influence healing atthe therapy site. In some embodiments a porous outer layer 330 may beformed of rotational spun PTFE.

In certain embodiments a relatively porous inner layer 325 may bedesirable. This layer may or may not be used in conjunction with asubstantially impermeable outer layer 330. A relatively porous innerlayer may permit tissue ingrowth and/or endothelial attachment or growthon the inside diameter of the stent 302 which may be desirable for anycombination of the following: healing, biocompatibility, prevention ofthrombosis, and/or reducing turbulent blood flow within the stent. Insome embodiments the inner layer may be comprised of a mat, such as arotational spun PTFE mat, having a percent porosity of about 40% toabout 80%, including about 50%; a thickness of about 20 micrometers toabout 100 micrometers, including from about 40 micrometers to about 80micrometers; and fiber diameters from about 50 nanometers to about 3micrometers.

Additionally or alternatively the mat may be comprised of a rotationalspun mat, such as PTFE, with an average pore size of about 1 micron toabout 12 microns, such as from about 2 microns to about 8 microns, orfrom about 3 microns to about 5 microns, or alternatively from about 3.5microns to about 4.5 microns.

FIG. 3B illustrates a cross sectional view of the stent 302 of FIG. 3A,again comprising a scaffolding structure 320 and covering comprising aninner layer 325, an outer layer 330, and a tie layer 335. Though in theillustration of FIG. 3B the tie layer 335 is shown at the same “level”as the scaffolding structure 320, the tie layer may be above or belowthe scaffolding in some embodiments. Further, as shown in FIG. 3B, eachlayer of the covering may be disposed so that there are no voids betweenlayers.

In some embodiments the tie layer 335 may be configured to promotebonding between the outer layer 330 and the inner layer 325. In otherembodiments the tie layer 335 may further be configured to providecertain properties to the stent 302 as a whole, such as stiffness ortensile strength. The tie layer 335 may thus be configured as areinforcing layer. In some embodiments, expanded PTFE (ePTFE) may beconfigured as a reinforcing layer. ePTFE may be anisotropic, havingdiffering properties in differing directions. For example, ePTFE maytend to resist creep in the direction the ePTFE membrane was expanded. Areinforcing layer of ePTFE may be oriented to increase strength, resistcreep, or impart other properties in a particular direction. ePTFE maybe oriented such that the expanded direction is aligned with an axialdirection of a medical device, a transverse direction, a radialdirection, at any angle to any of these directions, and so forth.Similarly, multiple layers of ePTFE may be disposed to increasestrength, resist creep, or impart other properties in multipledirections. The reinforcing layer may or may not be impermeable.

Additionally, in embodiments where both the inner layer 325 and theouter layer 330 are porous in nature, the tie layer 335 may beconfigured to create an impermeable layer between the two porous layers.In such embodiments the stent may permit tissue ingrowth, tissueattachment and/or healing on both the inner and outer surfaces of thestent while still preventing tissue outside of the stent from growinginto the lumen and occluding the lumen. Thus, tie layers may beconfigured to create a mid-layer portion of a construct, the tie-layerconfigured to inhibit tissue ingrowth into the layer or to be imperviousto tissue migration into or through the layer or to substantiallyinhibit tissue migration.

Furthermore, the tie layer 335 may be configured to be impervious orsubstantially impervious to fluid migration across the tie layer 335.Specifically, constructions comprising one or more porous layers mayallow fluid to cross the porous layer. In the case of a medicalappliance configured to control blood flow, such as a graft, a porouslayer may allow blood to leak across the layer or may allow certainsmaller components of the blood to cross the layer while containinglarger components, effectively filtering the blood. In some instancesthis filtration or ultrafiltration may allow components such as plasmato cross the barrier while containing red blood cells, leading toseroma. Thus, a fluid impermeable tie layer may be configured to containfluid within a medical device also comprised of porous layers. In somedevices, a tie layer may be both fluid impermeable and impervious totissue ingrowth, or may be configured with either of these propertiesindependent of the other. Constructs wherein any layer (other than, orin addition to a tie layer) is configured to be fluid impermeable and/orimpervious to tissue ingrowth are also within the scope of thisdisclosure. Thus, disclosure recited herein in connection with fluidimpermeable and/or tissue impervious tie layers may be analogouslyapplied to impermeable layers at various locations within a construct.

The tie layer (or any impermeable/impervious layer) may include anythermoplastic and may or may not be rotational spun. In one embodiment,the tie layer may be expanded PTFE. In another it may be rotational spunPTFE. In other embodiments it may be FEP, including rotational spun FEPand FEP applied as a film or dip coating. Furthermore, the tie layer mayinclude any of the following polymers or any other thermoplastic:dextran, alginates, chitosan, guar gum compounds, starch,polyvinylpyridine compounds, cellulosic compounds, cellulose ether,hydrolyzed polyacrylamides, polyacrylates, polycarboxylates, polyvinylalcohol, polyethylene oxide, polyethylene glycol, polyethylene imine,polyvinylpyrrolidone, polyacrylic acid, poly(methacrylic acid),poly(itaconic acid), poly(2-hydroxyethyl acrylate),poly(2-(dimethylamino)ethyl methacrylate-co-acrylamide),poly(N-isopropylacrylamide),poly(2-acrylamido-2-methyl-1-propanesulfonic acid),poly(methoxyethylene), poly(vinyl alcohol), poly(vinyl alcohol) 12%acetyl, poly(2,4-dimethyl-6-triazinylethylene),poly(3-morpholinylethylene), poly(N-1,2,4-triazolyethylene), poly(vinylsulfoxide), poly(vinyl amine), poly(N-vinyl pyrrolidone-co-vinylacetate), poly(g-glutamic acid), poly(Npropanoyliminoethylene),poly(4-amino-sulfo-aniline), poly[N-(p-sulphophenyl)amino-3-hydroxymethyl-1,4-phenyleneimino-1,4-phenylene],isopropyl cellulose, hydroxyethyl, hydroxylpropyl cellulose, celluloseacetate, cellulose nitrate, alginic ammonium salts, i-carrageenan,N-[(3′-hydroxy-2′,3′-dicarboxy)ethyl]chitosan, konjac glocomannan,pullulan, xanthan gum, poly(allyammonium chloride), poly(allyammoniumphosphate), poly(diallydimethylammonium chloride),poly(benzyltrimethylammonium chloride),poly(dimethyldodecyl(2-acrylamidoethyly)ammonium bromide),poly(4-N-butylpyridiniumethylene iodine),poly(2-N-methylpridiniummethylene iodine), poly(Nmethylpryidinium-2,5-diylethenylene), polyethylene glycol polymers andcopolymers, cellulose ethyl ether, cellulose ethyl hydroxyethyl ether,cellulose methyl hydroxyethyl ether, poly(1-glycerol methacrylate),poly(2-ethyl-2-oxazoline), poly(2-hydroxyethyl methacrylate/methacrylicacid) 90:10, poly(2-hydroxypropyl methacrylate),poly(2-methacryloxyethyltrimethylammonium bromide),poly(2-vinyl1-methylpyridinium bromide), poly(2-vinylpyridine N-oxide),poly(2-vinylpyridine), poly(3-chloro-2-hydroxypropyl2-methacryloxyethyldimethylammonium chloride), poly(4vinylpyridineN-oxide), poly(4-vinylpyridine),poly(acrylamide/2-methacryloxyethyltrimethylammonium bromide) 80:20,poly(acrylamide/acrylic acid), poly(allylamine hydrochloride),poly(butadiene/maleic acid), poly(diallyldimethylammonium chloride),poly(ethyl acrylate/acrylic acid), poly(ethyleneglycol)bis(2-aminoethyl), poly(ethylene glycol)monomethyl ether,poly(ethylene glycol)bisphenol A diglycidyl ether adduct, poly(ethyleneoxide-bpropylene oxide), poly(ethylene/acrylic acid) 92:8, poly(llysinehydrobromide), poly(1-lysine hydrobromide), poly(maleic acid),poly(n-butyl acrylate/2-methacryloxyethyltrimethylammonium bromide),poly(Niso-propylacrylamide),poly(N-vinylpyrrolidone/2-dimethylaminoethyl methacrylate), dimethylsulfatequaternary, poly(N-vinylpyrrolidone/vinyl acetate),poly(oxyethylene)sorbitan monolaurate (Tween 20®), poly(styrenesulfonicacid), poly(vinyl alcohol), N-methyl-4(4′formylstyryl)pyridinium,methosulfate acetal, poly(vinyl methyl ether), poly(vinylamine)hydrochloride, poly(vinylphosphonic acid), poly(vinylsulfonic acid)sodium salt, and polyaniline.

Regardless of the material, the tie layer 335 may or may not berotational spun. Further, in certain embodiments the stent 302 mayinclude two or more tie layers. The tie layer 335 may be formed in anymanner known in the art and attached to the inner 325 and outer 330layers in any manner known in the art. For example, the tie layer 335may comprise a sheet of material which is wrapped around the inner layer325 or a tube of material which is slipped over the inner layer 325which is then heat shrunk or otherwise bonded to the inner 325 and outer330 layers. Further, in embodiments where the tie layer is rotationalspun, it may be rotational spun directly onto the inner layer 325, thescaffolding, or both. In some instances the tie layer 335 may be meltedafter the stent 302 is constructed to bond the tie layer 335 to adjacentlayers of the stent covering.

Furthermore, tie layers may be configured to change the overallproperties of the medical appliance. For example, in some instances acover or construct comprised solely of rotational spun PTFE (of thedesired pore size) may not have desired tensile or burst strength. A tielayer comprised of a relatively stronger material may be used toreinforce the PTFE inner layer, the PTFE outer layer, or both. Forexample, in some instances FEP layers may be used to increase thematerial strength of the cover. Again, as discussed above, the tie layermay also be configured as a portion of the construct configured to beimpervious to tissue ingrowth or migration.

Further, one or more layers of rotational spun PTFE may be used inconnection with a scaffolding structure other than that shown herein. Inother words, the disclosure above relating to covers, layers, tielayers, and related components is applicable to any type of scaffoldingstructure as well as to stents or grafts with no separate scaffoldingstructure at all.

FIGS. 4A-4E illustrate certain steps in a process of manufacturing amultilayer construct for use in connection with a medical appliance.More specifically, these figures illustrate a process of creating astent covered with rotational spun material. Again, this disclosure isequally relevant to all medical appliances which may comprise a cover ormultilayered construct, including grafts, patches, stents, and so on.Additionally, as suggested in the additional examples disclosed below,the illustrated steps may be optional in some instances or augmented byadditional steps in others.

FIG. 4A illustrates a covering inner layer 425 disposed around a mandrel416. As described above, the inner layer 425 may be rotational spundirectly onto the mandrel 416, including instances wherein the mandrel416 was rotating during the process. In the illustrated embodiment, theinner layer 425 was rotational spun onto a rotating mandrel 416 suchthat the resultant tube of material has no seam. After the inner layer425 is rotational spun onto the mandrel 416, the inner layer 425 maythen be sintered. In the case of PTFE, the membrane may be sintered attemperatures of about 385 degrees C., including temperatures from about360 degrees C. to about 400 degrees C. Sintering may tend to set thestructure of the PTFE, meaning sintering reduces the softness orflowability of the PTFE. Furthermore, as discussed above, sintering orotherwise heat treating the mat may evaporate any water or PEO mixedwith the PTFE, resulting in a material comprised substantially of purePTFE.

Once the inner layer 425 is sintered, the tube of material may beremoved from the mandrel 416, as illustrated in FIG. 4B. As shown in theillustrated embodiment, the inner layer 425 may be “peeled” from themandrel 416 to initially break any adherence of the inner layer 425 tothe mandrel 416. The inner layer 425 may also be removed by pushing thecovering with respect to the mandrel 416, causing the material to bunchas it is removed from the mandrel 416. In some embodiments, low frictioncoatings may alternatively or additionally be applied to the mandrel 416before the inner layer 425 is rotational spun. The inner layer 425 maythen be reapplied to the mandrel 416, by slipping the inner layer 425over the mandrel 416, as illustrated in FIG. 4C.

Once the inner layer 425 is reapplied to the mandrel 416, a wirescaffolding 420 can be formed over the mandrel 416 and the inner layer425, as shown in FIG. 4D. FIG. 4E illustrates an outer layer 430 ofmaterial which may then be rotational spun onto the scaffolding 420 andthe inner layer 425. The entire construct may then be sintered.Additional layers may also be added through similar processes.

Many variations to the above-described process are within the scope ofthe present disclosure. For example, one or more layers may be appliedby wrapping strips or mats of material around the mandrel 416 and/or theother layers. Further, some of the layers may be applied by spray or dipcoating the mandrel 416 and/or the other layers. It is within the scopeof this disclosure to vary the process above to apply to any of thelayers, or any additional layers, using any method disclosed herein.

In another example, a stent may be comprised of an inner layer ofrotational spun PTFE, a tie layer of FEP, and an outer layer of PTFE.The properties of each of these layers, including percent porosity, matthickness, fiber diameter, and/or average pore size may be controlled toform a covering layer that inhibits the growth of tissue into or througha particular layer or that permits endothelial growth or attachment on aparticular layer.

In some such embodiments, the inner layer of PTFE may be spun on amandrel, sintered, removed from the mandrel, and replaced on the mandrelthen a scaffolding structure applied around the inner layer (analogousto the procedure illustrated in FIGS. 4A-4D). The FEP tie layer may thenbe applied by dipping, spraying, applying a film layer, electrospinning,rotational spinning, extrusion, or other processing.

In some embodiments, the FEP layer may be heated such that the FEPbecomes soft, in some cases flowing into open spaces in adjacent PTFElayers. This may tie the FEP layer to adjacent PTFE layers. In someinstances, heating the construct to about 325 degrees C. may allow theFEP to partially flow into openings in adjacent PTFE layers, without theFEP completely flowing through the PTFE mat. FIG. 20 and Example 10,included below, provide one example of an FEP layer partially meltinginto a rotational spun PTFE mat.

In another particular example, an inner layer of PTFE may be rotationalspun on a mandrel, sintered, removed, and replaced, then a scaffoldingstructure applied around the inner layer. An FEP tie layer may then beapplied as a film layer. In some instances this tie layer may be“tacked” into place, for example, by a soldering iron. A tube of PTFE(which may be formed separately by rotational spinning onto a mandreland sintering) may then be disposed over the FEP film layer. The entireconstruct may then be pressured, for example, by applying a compressionwrap. In some embodiments this wrap may comprise any suitable material,including a PTFE-based material. In other embodiments a Kapton film maybe wrapped around the construct before the compression wrap, to preventthe construct from adhering to the compression wrap.

The compressed layers may then be heated above the melting temperatureof the FEP tie layer, but below the sintering temperature of the PTFE.For example, the melt temperature of the FEP may be from about 264degrees C. to about 380 degrees C., including about 325 degrees C. PTFEmay be sintered at temperatures from about 360 degrees C. to about 400degrees C. Thus, the entire construct may be heated to an appropriatetemperature such as about 325 degrees C. In some embodiments theconstruct may be held at this temperature for about 15 to about 20minutes. Heating the FEP layer to about 325 degrees C. may allow the FEPlayer to remain substantially impervious to tissue ingrowth and/orattachment, creating a “barrier” layer within the construct, while stilladhering the FEP to adjacent layers of PTFE. In other embodiments,heating the construct to higher temperatures, such as about 350 degreesC. or more may be configured to allow the FEP to flow around the PTFEsuch that the entire construct has a higher degree of porosity and theFEP layer is not as impervious to ingrowth.

The joining of the FEP tie layer to the PTFE outer and inner coverlayers may increase the strength of the finished covering. The constructmay then be cooled and the compression wrap and the Kapton filmdiscarded. The construct may then be removed from the mandrel.

A stent formed by the exemplary process described above may beconfigured with desired characteristics of porosity and strength. Insome instances the FEP material may coat the PTFE nanofibers but stillallow for sufficient porosity to permit tissue ingrowth and/orendothelial attachment or growth. The degree to which the FEP coats thePTFE may be controlled by the temperature and time of processing. Thelower the temperature and/or the shorter the time the construct is heldat temperature, the less the FEP may flow. In some instances a tie layerof FEP which is impervious to tissue ingrowth into or through the layermay be formed by heating the construction only to about 270 degrees C.

FIG. 5 illustrates a stent 502 which comprises a scaffolding structure520 and a covering 524. The covering 524 may be comprised of anycombination of layers disclosed herein. Additionally, the stent 502 ofFIG. 5 includes a cuff 540 at both ends of the stent 502. In otherembodiments a cuff 540 may only be located at one end of the stent 502.

The cuff 540 may comprise an additional covering layer on the outsidediameter of the stent 502, disposed adjacent to one or both ends of thestent 502. The cuff 540 may be configured to promote tissue ingrowth,attachment, and/or incorporation into the cuff 540; for example the cuff540 may be more porous than an outer layer of the covering 524 of thestent 502. Factors such as porosity, type of covering or coating, typeof material, use of organic material, and/or use or composite materialsformed of synthetic material and organic material may be used to createa cuff 540 configured for tissue ingrowth. Again, the cuff 540 may beconfigured to promote tissue ingrowth and/or the growth or attachment ofendothelial cells at one or both ends of the stent 502. When implantedin the body, the cuffs 540 may tend to “anchor” the ends of the stent502 with respect to the vessel walls, reducing the relative movement ofthe stent ends with respect to the vessel walls. Such a reduction inmovement may lessen irritation of the vessel by the stent ends,minimizing complications such as stenosis. Cuffs 540 may be configuredfor use in CVO type applications in some instances. Furthermore, a bandof porous material analogous to the stent cuff 540 illustrated may becoupled to any medical appliance to anchor a portion of such a device.

In some embodiments, the outer layer of the covering 524 of the stent502 may be relatively non-porous to inhibit tissue ingrowth into orthrough the outer layer, but the cuff 540, disposed about the outerlayer, may provide a section near each end at which some tissueingrowth, attachment, or incorporation may occur.

The cuff 540 may be comprised of a rotational spun material, such asPTFE, and may be bonded to the outer covering layer through any method,including methods of multilayer device construction described herein.For example, a layer of FEP may be disposed between the outer coveringlayer and the cuff 540 and heated to bond the layers. In otherembodiments the cuff 540 may comprise a collagen layer which is coupledto the stent. Further, a co-rotational spun collagen and PTFE cuff 540may be utilized.

The current disclosure relates to medical appliances, including stents,which may comprise a frame structure provided in connection with one ormore coverings or coatings. It will be appreciated that, thoughparticular structures, coverings, and coatings are described herein, anyfeature of the frames or coverings and/or coatings described herein maybe combined with any other disclosed feature without departing from thescope of the current disclosure. For example, certain figures referencebelow show a metal frame without any covering or coating; the featuresdescribed and illustrated in those figures may be combined with anycombination of coverings or coatings disclosed herein. Further, as usedherein, the term “frame” refers to a support structure for use inconnection with a medical appliance. For instance, a scaffoldingstructure, such as that described in connection with FIGS. 4A-4E, above,is an example of a frame used in connection with a medical appliance. Insome embodiments, a medical appliance—such as a stent—may comprise framealone, with no covering, coating, or other components.

Moreover, the current disclosure is applicable to a wide variety ofmedical appliances which may utilize any of the rotational spun matsdisclosed herein, including medical appliances which comprisemultilayered constructs. For example, a hernia patch may comprise a twolayered construction, which one side of the patch configured to allowtissue ingrowth and/or attachment (for bonding and healing) and theother side configured to resist such ingrowth and/or attachment (to makethe second side “slippery” with respect to surrounding tissue. Further,a patch as described above may also comprise a tie layer disposedbetween the two exterior layers. The tie layer may be configured resisttissue ingrowth or attachment into or through the patch and/or toprovide mechanical properties such as strength to the construct.

FIGS. 6, 7A, and 7B show views of a possible embodiment of a frame foruse in connection with a medical appliance such as a stent or graft.FIG. 7C is an alternative configuration of a portion of the framestructure. FIGS. 8 and 9 are views of one embodiment of a frame whichincludes flared ends. FIG. 10 illustrates one embodiment of how a wiremay be shaped to form a frame.

Frames for use in connection with medical appliances may be fabricatedor formed into particular geometries through a variety of means. Forexample, a frame may be cut from a single tube of material, includingembodiments wherein the frame is first laser cut, then expanded. Inother embodiments, the frame may be molded, including embodimentswherein the frame is molded from a polymeric material. In still otherembodiments, powder metallurgical processes, such as powderedcompression molding or direct metal laser sintering, may be used.

FIG. 6 illustrates a front elevation view of an embodiment of a frame.The illustrated embodiment depicts one embodiment of a configuration fora metal wire 650 forming a frame. As depicted in FIG. 6, the frame mayconsist of a single continuous wire.

Referring generally to FIGS. 6, 7A, and 7B, particular features of theillustrated frame structure are indicated. It will be appreciated thatthe numerals and designations used in any figure apply to analogousfeatures in other illustrated embodiments, whether or not the feature isso identified in each figure. As generally shown in these Figures, theframe structure may consist of a wire 650 shaped to form the frame. Thewire 650 may be shaped in a wave-type configuration, the waves definingapexes 652 and arms 654 of the frame structure. The frame may further becoupled to a covering layer (not pictured). Additionally, in someembodiments, any covering as disclosed herein may be applied to any typeof frame, for example, laser cut frames, polymeric frames, wire frames,and so forth.

The frame may be designed such that the midsection is “harder” than theends. The “hardness” of the frame refers to the relative strength of thestructure (e.g., its compressibility). A harder portion of the framewill have greater strength (i.e., exert a greater radial outward force)than a softer portion. In one embodiment, the midsection is harder thanthe proximal and distal end sections which are relatively softer.Further, a frame may be configured to be flexible to facilitate theability of the device to conform to the native anatomy at which thedevice is configured for use. Similarly, covered devices may beconfigured with covers which conform to the native anatomy at a therapysite.

Additionally, the frame may be configured to allow the entire device tobe crimped into a relatively low-profile configuration for delivery. Forexample, devices of a certain diameter or constrained profile are morefeasible for delivery at certain vascular or other access points thanothers. For example, in many instances a device configured for insertionvia the radial artery may be relatively smaller than devices configuredfor insertion via the generally larger femoral artery. A frame may beconfigured to be crimped into a particular profile to enable potentialaccess at various or desired access points. Similarly, devices having noframe may be configured to be disposed in a particular profile tofacilitate access and delivery. Once a device is positioned within thebody it may be expanded or deployed in a number of ways, including useof self expanding materials and configurations. Additionally, someconfigurations may be designed for expansion by a secondary device, suchas a balloon.

Four basic design parameters may be manipulated to influence theproperties (hardness, strength, crush force, hoop force, flexibility,etc.) of the illustrated frame. These properties are: (1) apex to apexdistance, designated as H_(x) in FIGS. 6 and 7A; (2) arm length,designated as A_(x) in FIGS. 6 and 7A; (3) apex radius, designated asR_(x) in FIG. 7A; and (4) the diameter of the wire 650. These values mayor may not be constant at different points on a frame. Thus, thesubscript “x” is used generically; that is, each distance identified as“H” refers to an apex to apex distance with subscripts 1, 2, 3, etc.,signifying the apex to apex distance at a particular point. It will beappreciated that these subscript designations do not necessarily referto a specific distance, but may be used relatively (i.e., H₁ may bedesignated as smaller than H₂ without assigning any precise value toeither measurement). Further, as will be apparent to one skilled in theart having the benefit of this disclosure, an analogous pattern ofmeasurements and subscripts is employed for other parameters describedherein, for example A_(x) and R_(x).

The overall frame design may be configured to optimize desired radialforce, crush profile, and strain profile. The frame design parametersmay each be configured and tuned to create desired characteristics. Forexample, the strain profile may be configured to be less than thefailure point for the material being used.

A first parameter, the apex to apex distance, is designated as H_(x).This measurement signifies the distance between a first apex and asecond apex where both apexes substantially lie along a line on theoutside diameter of the frame which is co-planar with, and parallel to,the longitudinal axis of the frame. In some embodiments, H_(x) may beconstant along the entire length of the frame. In other embodiments thelength of the frame may be divided into one or more “zones” where H_(x)is constant within a zone, but each zone may have a different H_(x). Instill other embodiments H_(x) may vary along the entire length of theframe. H_(x) may be configured, in connection with the other designparameters, to determine the properties of the frame. Generally, regionsof the frame with a smaller H_(x) value will be harder than regions witha larger H_(x) value.

In the embodiment illustrated in FIG. 6, there are two “flare zones” ateither end of the frame and a midbody zone along the remaining length ofthe frame. In the illustrated embodiment, H₁ designates the apex to apexdistance in the midbody zone of the frame and H₂ designates the apex toapex distance in the flare zones of the frame. In the illustratedembodiment, the apex to apex distance, H₂, is the same in both the flarezone near the distal end of the frame and the flare zone near theproximal end of the frame. In some embodiments H₁ may be smaller thanH₂, resulting in a frame that is relatively harder in the midbody andrelatively softer on the ends. A frame with such properties may beutilized in applications where strength is necessary along the midbody,for example to treat a tumor or other occlusion, but the ends areconfigured to rest on healthy tissue where softer ends will minimizetrauma to the healthy tissue.

In embodiments where soft ends and a hard midbody are desirable, H₁ maybe between about 2 mm and 30 mm, and H₂ between about 2.1 mm and 30.1mm. For example, in frames configured for use in connection with stentsfor CV or PV application, H₁ may be between about 3 mm and 10 mm, and H₂between about 3.1 mm and 10.1 mm, such as: 3 mm<H₁<8 mm and 3.5 mm<H₂<9mm; 3 mm<H₁<6.5 mm and 4 mm<H₂<8 mm; or 3 mm<H₁<5 mm and 5.5 mm<H₂<6.5mm.

In other embodiments where two or more apex to apex lengths are presentin one frame, the change in apex to apex length may be correlated to thedisplacement of the apexes from the midpoint of the frame. In otherwords, the apex to apex length may increase incrementally as one movesaway from the midpoint of the frame toward the ends in a manner thatgives the frame the same geometry, and therefore the same properties, oneither side of the midpoint of the length of the frame. In otherembodiments, different geometries may be utilized at any point along thelength of the frame. It will be appreciated that the ranges of valuesfor H_(x) disclosed above apply analogously to embodiments where theframe has multiple apex to apex lengths. For example, in one embodimenta frame may have an apex to apex length at midbody within one of theranges disclosed above for H₁, and the value of H_(x) may varyincrementally, in steps, or some other pattern, along the length of theframe reaching an apex to apex length at the ends within thecomplementary range for H₂.

Moreover, in some embodiments, the value of H_(x) may be small enoughthat adjacent coils are “nested” within each other. In other words, theapexes of a first helical coil may extend up into the spaces just belowthe apexes of the next adjacent coil. In other words, apexes of lowercoils may extend a sufficient amount so as to be disposed between thearms of higher coils. In other embodiments the value of H_(x) may belarge enough that adjacent coils are completely separated. Inembodiments wherein adjacent coils are “nested,” the number of wires atany particular cross section of the stent may be higher than anon-nested stent. In other words, cutting the frame along an imaginaryplane disposed orthogonally to the longitudinal axis of the frame willintersect more wires if the frame is nested as compared to not nested.The smaller the value of H_(x), the more the rows may be intersected bysuch a plane (that is, more than just the next adjacent row may extendinto the spaces below the apexes of a particular row). Nested frames maycreate relatively higher strains in the frame when a stent comprised ofthe frame is loaded into a delivery catheter. In some instances thedelivery catheter for a nested frame may therefore be relatively largerthan a delivery catheter configured for a non-nested frame. Further,nested frames may be relatively stiff as compared to non-nested stentswith similar parameters.

As will be apparent to those skilled in the art having the benefit ofthis disclosure, frames with a hard midbody and soft ends may bedesirable for a variety of applications. Further, in some instances abasically “symmetric” frame may be desirable; in other words, a framewith certain properties at the midbody section and other properties atthe ends, where the properties at both ends are substantially identical.Of course, other embodiments may have varied properties along the entirelength of the frame. It will be appreciated that while the effect ofchanging variables, for instance the difference between H₁ and H₂, maybe described in connection with a substantially symmetric stent (as inFIG. 6) the same principles may be utilized to control the properties ofa frame where the geometry varies along the entire length of the frame.As will be appreciated by those skilled in the art having the benefit ofthis disclosure, this applies to each of the variable parametersdescribed herein, for example H_(x), A_(x), and R_(x).

A second parameter, arm length, is designated as A_(x) in FIGS. 6 and7A. As with H_(x), A_(x) may be constant along the length of the frame,be constant within zones, or vary along the length of the frame.Variations in the length of A_(x) may be configured in conjunction withvariations in the other parameters to create a frame with a particularset of properties. Generally, regions of the frame where A_(x) isrelatively shorter will be harder than regions where A_(x) is longer.

In some embodiments, the arm length A₁ near the midsection of the framewill be shorter than the arm length A₂ near the ends. This configurationmay result in the frame being relatively harder in the midsection. Inembodiments where soft ends and a hard midbody are desirable, A₁ may bebetween about 2 mm and 30 mm, and A₂ between about 2.1 mm and 30.1 mm.For example, in frames for CV or PV application, A₁ may be between about2 mm and 10 mm, and A₂ between about 2.1 mm and 10.1 mm, such as: 2.5mm<A₁<8 mm and 3 mm<A₂<9 mm; 3 mm<A₁<6 mm and 4 mm<A₂<7.5 mm; or 4mm<A₁<5 mm and 5 mm<A₂<6 mm.

In other embodiments where two or more arm lengths are present in oneframe, the change in arm length may be correlated to the displacement ofthe arm from the midpoint along the frame. In other words, the armlength may increase incrementally as one moves away from the midpoint ofthe frame toward the ends in a manner that gives the frame the samegeometry, and therefore the same properties, on either side of themidpoint of the length of the frame. In other embodiments, differentgeometries may be utilized at any point along the length of the frame.It will be appreciated that the ranges of values for A_(x) disclosedabove apply analogously to embodiments where the frame has multiple armlengths. For example, in one embodiment a frame may have an arm lengthat midbody within one of the ranges disclosed above for A₁, and thevalue of A_(x) may vary incrementally, in steps, or some other pattern,along the length of the frame reaching an arm length at the ends withinthe complementary range for A₂.

A third parameter, the apex radius, is designated as R₁ in FIG. 7A. Aswith H_(x), and A_(x), R_(x) may be configured in order to createdesired properties in a frame. In some embodiments, the inside radius ofeach apex may form an arc which has a substantially constant radius. Asshown by a dashed line in FIG. 7A, this arc can be extended to form acircle within the apex. The measurement R_(x) refers to the radius ofthe arc and circle so described. Further, in some embodiments the armsand apexes of the frame are formed by molding a wire around pinsprotruding from a mandrel. The radius of the pin used gives the apex itsshape and therefore has substantially the same radius as the apex. Insome embodiments R_(x) will be constant along the entire length of theframe, be constant within zones along the length of the frame, or varyalong the entire length of the frame. Variations in the magnitude ofR_(x) may be configured in conjunction with variations in the otherparameters to create a frame with a particular set of properties.Generally, regions of the frame where R_(x) is relatively smaller willbe harder than regions where R_(x) is larger.

Furthermore, in some instances, smaller values of R_(x) may result inrelatively lower strain in the wire frame when the frame is compressed,for example when the frame is disposed within a delivery catheter.Moreover, wires of relatively larger diameters may result in relativelylower strain at or adjacent to the radius measured by R_(x) whencompressed, as compared to wires of smaller diameters. Thus, in someinstances, the strain may be optimized for a particular design byvarying the value of R_(x) and the diameter of the wire forming theframe.

Like the other variables, R_(x) may take on a range of values dependingon the application and the desired properties of the frame. In someembodiments R_(x) may be between about 0.12 mm and 1.5 mm, includingfrom about 0.12 to about 0.64 mm. For example, in frames configured foruse with stents for CV or PV application, R_(x) may be between about0.35 mm and 0.70 mm, such as: 0.35 mm<R_(x)<0.65 mm; 0.35 mm<R_(x)<0.6mm; or 0.4 mm<R_(x)<0.5 mm.

It will be appreciated that the disclosed ranges for R_(x) apply whetherthe value of R_(x) is constant along the length of the frame, whetherthe frame is divided into zones with different R_(x) values, or whetherR_(x) varies along the entire length of the frame.

The fourth parameter, wire diameter, is discussed in detail inconnection with FIG. 10 below.

FIG. 7A illustrates a cutaway view of the front portions of two adjacentcoils of a frame. The portions of the coils depicted are meant to beillustrative, providing a clear view of the three parameters H_(x),A_(x), and R_(x). It will be appreciated that all three of theseparameters may be configured in order to create a frame with particularproperties. Any combination of the values, ranges, or relativemagnitudes of these parameters disclosed herein may be used within thescope of this disclosure. As an example of these values taken together,in one embodiment of a CV or PV frame with a relatively hard midbody andsofter ends, H₁ may be about 4 mm and H₂ about 5.9 mm; A₁ may be about4.5 mm and A₂ about 5.6 mm; and R₁ about 0.5 mm.

FIG. 7B is a close up view of one end of a frame. In embodiments wherethe frame is formed by a single continuous wire, FIG. 7B illustrates oneway in which the end 656 of the wire may be coupled to the frame. Asillustrated, the wire may be disposed such that the final coilapproaches and runs substantially parallel to the previous coil. Thisconfiguration results in the apex to apex distance between the two coilsdecreasing near the end 656 of the wire. In some embodiments thistransition will occur along the distance of about 4 to 8 apexes alongthe length of the wire. For example, if a frame is configured with anapex to apex spacing of H₂′ along the region of the frame nearest to theends, the apex to apex distance will decrease from H₂′ to a smallerdistance which allows the end 656 of the wire to meet the prior coil (asillustrated in FIG. 7B) over the course of about 4 to 8 apexes.

FIG. 7C illustrates an alternative configuration of a portion of aframe. In the embodiment of FIG. 7C, apexes 652′ alternate in relativeheight along the length of the wire. In particular, in the embodimentshown, the apexes form a pattern comprising a higher apex, a shorterapex, a higher apex, a shorter apex, and so on, around the helical coil.In some instances, a frame may be configured with alternating apexes atone or both ends of the frame. For example, a frame as shown in FIG. 6may be configured with the pattern of apexes 652′ and arms 654′ shown inFIG. 7C at one or both ends of the frame. Such an alternating pattern ofapexes may distribute the force along the vessel wall at the ends of theframe, thus creating relatively a-traumatic ends.

The end 656 may be attached to the frame in a variety of ways known inthe art. The end 656 may be laser welded to the frame or mechanicallycrimped to the frame. In embodiments where the frame is an element of amedical appliance further comprising a polymer cover, the end 656 may besecured by simply being bound to the cover. In other instances, a stringmay be used to bind or tie the end 656 to adjacent portions of theframe. Similarly, in some instances, a radiopaque marker may be crimpedaround the end 656 in such a manner as to couple the end 656 to theframe. Additionally other methods known in the art may be utilized.

Furthermore, in some embodiments the frame may be configured withradiopaque markers at one or more points along the frame. Such markersmay be crimped to the frame. In other embodiments a radiopaque ribbon,for example a gold ribbon, may be threaded or applied to the frame. Insome embodiments these markers may be located at or adjacent to one orboth ends of the frame. Any radiopaque material may be used, for examplegold or tantalum. Radiopaque elements may be configured to facilitatethe delivery and placement of a device and/or to facilitate viewing ofthe device under fluoroscopy.

Referring again to FIG. 6 as well as to FIGS. 8 and 9, the frame may beconfigured with flared ends. It will be appreciated that in certainembodiments a frame may have a flare at both the proximal and distalends, only at the proximal end or only at the distal end, or at neitherend. In certain of these embodiments the frame may have a substantiallyconstant diameter in the midbody zone of the frame, with the endsflaring outward to a larger diameter. It will be appreciated that thegeometry of the flares at the proximal and distal ends may or may not bethe same.

In the embodiment illustrated in FIG. 6, the frame has a diameter, D₁,at the midbody of the frame. This diameter may be constant along theentire midbody of the frame. The illustrated embodiment has a seconddiameter, D₂, at the ends. This change in diameter creates a “flarezone” at the end of the frame, or an area in which the diameter isincreasing and the frame therefore may be described as including a“flared” portion. In some embodiments the flare zone will be from about1 mm to 60 mm in length. For example in certain frames configured foruse with stents designed for CV or PV application, the flare zone may befrom about 3 mm to about 25 mm in length, such as: from about 4 mm toabout 15 mm, or from about 5 mm to about 10 mm in length.

The diameter of the stent at the midbody, the diameter at one or bothflares, or all of these dimensions, may be configured to be slightlylarger than the body lumen for in which the device is configured foruse. Thus, the size of the device may cause interference with the lumenand reduce the likelihood the device will migrate within the lumen.Further, active anti-migration or fixation elements such as barbs oranchors may also be used.

FIGS. 8 and 9 also illustrate how a frame may be flared at the ends.Diameters D₁′ and D₁″ refer to midbody diameters, analogous to D₁, whileD₂′ and D₂″ refer to end diameters analogous to D₂. Further, asillustrated in FIG. 9, the flared end may create an angle, alpha,between the surface of the frame at the midbody and the surface of theflare. In some instances the flare section will uniformly flare out at aconstant angle, as illustrated in FIG. 9. In some embodiments anglealpha will be from about 1 degree to about 30 degrees. For example, insome frames configured for use with stents designed for CV or PVapplication, alpha will be from about 2 degrees to 8 degrees, such as:from about 2.5 degrees to about 7 degrees or from about 3 degrees toabout 5 degrees. In one exemplary embodiment, alpha may be about 3.6degrees.

The frame of FIG. 6 also has a length L. It will be appreciated thatthis length can vary depending on the desired application of the frame.In embodiments where the frame has flare zones at the ends, longerframes may or may not have proportionally longer flare zones. In someembodiments, this flare zone may be any length described above,regardless of the overall length of the frame.

The disclosed frame may be formed in a variety of sizes. In someembodiments, L may be from about 10 mm to about 200 mm. For example, inCV applications the frame may have a length, L, of from about 40 mm to100 mm or any value between, for example, at least about 50 mm, 60 mm,70 mm, 80 mm, or 90 mm. In PV applications the frame may have a length,L, of from about 25 mm to 150 mm or any value between, for example atleast about 50 mm, 75 mm, 100 mm, or 125 mm. The frame may also belonger or shorter than these exemplary values in other applications.

Likewise the frame may be formed with a variety of diameters. In someembodiments the midbody diameter of the frame may be from about 1 mm toabout 45 mm, including from about 4 mm to about 40 mm. For example, inCV or PV applications the frame may have a midbody inside diameter ofabout 3 mm to 16 mm, or any distance within this range such as betweenabout 5 mm and about 14 mm or between about 7 mm and about 10 mm.Moreover, in some instances, the diameter, or a diameter-likemeasurement of the frame may be described as a function of othercomponents. For example, the frame may be configured with a particularnumber of apexes around a circumference of the frame. For example, someframes may be configured with between about 2 and about 30 apexes arounda circumference of the frame.

The frame may or may not be configured with flared ends regardless ofthe midbody diameter employed. In some CV embodiments the maximumdiameter at the flared end will be between about 0.5 mm and about 2.5 mmgreater than the midbody diameter. For example, the maximum diameter atthe flared end may be between about 1 mm and about 2 mm, oralternatively between about 1.25 mm and about 1.5 mm, such as about 1.25mm or about 1.5 mm greater than the midbody diameter.

Referring now to FIG. 10, the frame may be formed from a singlecontinuous wire. In some embodiments the wire may be comprised ofNitinol (ASTM F2063), or other suitable materials. In some embodimentsthe wire will have a diameter between about 0.001 inch and about 0.05inch, including from about 0.005 inch and about 0.025 inch. For example,in some frames designed for CV or PV application, the wire diameter maybe from about 0.008 inch to about 0.012 inch in diameter includingcertain embodiments where the wire is from about 0.009 inch to about0.011 inch in diameter or embodiments where the wire is about 0.010 inchin diameter. Furthermore, frames configured for the thoracic aorta maybe formed of wires up to 0.020 inch in diameter, including wires betweenabout 0.010 inch and 0.018 inch in diameter.

FIG. 10 illustrates how, in some embodiments, the wire 650 may be woundin a helical pattern creating coils that incline along the length of thestent. The waves of the wire which form the arms and apexes may becentered around this helix, represented by the dashed line 660.

In some embodiments, a stent, graft, or other tubular device maycomprise a tapered segment along the length of the device. A taper maybe configured to reduce the velocity of fluid flow within the device asthe fluid transitions from a smaller diameter portion of the device to alarger diameter portion of the device. Reducing the fluid velocity maybe configured to promote laminar flow, including instances wherein atubular member is tapered to promote laminar flow at the downstream endof the device.

Further, in some embodiments, a stent or other tubular member may bepositioned at a junction between two or more body lumens. For example,FIG. 23A illustrates a stent 702 a disposed at an intersection betweentwo body lumens. In some embodiments, stent 702 a may be configured topromote laminar flow at the intersection of the lumens.

FIG. 23B illustrates a portion of a stent 702 b having a tapered segment705 b which may be configured to reduce flow velocity within the stent702 b. In some embodiments, such as that of FIG. 23B, the taperedsegment 705 b may be positioned upstream of the downstream end of thestent 702 b. FIG. 23C illustrates another exemplary embodiment of aportion of a stent 702 c having a tapered segment 705 c adjacent thedownstream end of the stent 702 c. Either tapered segment (705 b, 705 c)may be used in connection with any stent, including embodiments whereinthe tapered segment is configured to promote laminar flow in and aroundthe stent. For example, the stent 702 a of FIG. 23A may be configuredwith either tapered portion (705 b, 705 c) to promote laminar flow outof the stent 702 a and at the junction between the body lumens of FIG.23A.

Use of rotational spun coatings may facilitate application of a coveringof uniform thickness along a tapered stent. For example, in someembodiments, rotational spun coatings may be configured to evenly coatdevices comprised of various geometries. A rotational spun coating maydeposit a substantially even coating along various geometries such astapers, shoulders, and so forth.

EXAMPLES

A number of exemplary PTFE mats were produced according to thedisclosure above. FIGS. 11A-20 are SEMs of the PTFE mats produced ineach exemplary process. The following examples are intended to furtherillustrate exemplary embodiments and are not intended to limit the scopeof the disclosure.

Example 1

A 60 wt % PTFE water dispersion was mixed with PEO and water as follows.Water was added to PEO to maintain a ratio of 2.86 ml of water per gramof PEO. The water and PEO were mixed until the PEO was fully dissolvedand the solution created a thick gel. 25.71 ml of 60 wt % PTFE aqueousdispersion was added to the dissolved PEO to obtain a 0.05 g/ml mixtureof PEO to PTFE dispersion. The mixture was strained through a 70micrometer or finer filter to remove any large particles. The combinedsolution was then allowed to sit and/or mixed in a non-agitating jarroller until the solution achieved homogeneity; in some instances thatprocess takes 24 to 48 hours.

The combined solution was then rotational spun from a spinneret at about3000 RPM and collected on a 2 inch by 2 inch sheet of aluminum foil. Thecollection sheet was positioned about 10 inches from the spinneret. Theorifices on the spinneret were about 30 gauge openings. The mat was thensintered at about 385 degrees C. for about 10 minutes.

Small beads were observed on the fibers produced in this example. Theresultant mat was about 50 micrometers thick. It was further observedthat the mat was generally very open. Similarly, the fiber diametersobserved were generally small to medium in diameter.

FIG. 11A is an SEM of the rotational spun PTFE mat created in theprocedure of Example 1. FIG. 11A reflects a magnification of 170×. FIG.11B is an SEM of the rotational spun PTFE of FIG. 11A at a magnificationof 950×.

Example 2

A 60 wt % PTFE water dispersion was mixed with PEO and water as follows.Water was added to PEO to maintain a ratio of 2.86 ml of water per gramof PEO. The water and PEO were mixed until the PEO was fully dissolvedand the solution created a thick gel. 24.00 ml of 60 wt % PTFE aqueousdispersion was added to the dissolved PEO to obtain a 0.07 g/ml mixtureof PEO to PTFE dispersion. The mixture was strained through a 70micrometer or finer filter to remove any large particles. The combinedsolution was then allowed to sit and/or mixed in a non-agitating jarroller until the solution achieved homogeneity; in some instances thatprocess takes 24 to 48 hours.

The combined solution was then rotational spun from a spinneret at about4500 RPM and collected on a 2 inch by 2 inch sheet of aluminum foil. Thecollection sheet was positioned about 9.5 inches from the spinneret. Theorifices on the spinneret were about 30 gauge openings. The mat was thensintered at about 385 degrees C. for about 10 minutes.

The generally random deposition of the fibers as well as theintersecting or crossing nature of fibers may be seen in this example.The resultant mat was about 50 micrometers thick. It was furtherobserved that the mat was generally open. Similarly, the fiber diametersobserved were generally of medium diameter.

FIG. 12A is an SEM of the rotational spun PTFE mat created in theprocedure of Example 2. FIG. 12A reflects a magnification of 170×. FIG.12B is an SEM of the rotational spun PTFE of FIG. 12A at a magnificationof 950×.

Example 3

A 60 wt % PTFE water dispersion was mixed with PEO and water as follows.Water was added to PEO to maintain a ratio of 2.86 ml of water per gramof PEO. The water and PEO were mixed until the PEO was fully dissolvedand the solution created a thick gel. 24.00 ml of 60 wt % PTFE aqueousdispersion was added to the dissolved PEO to obtain a 0.07 g/ml mixtureof PEO to PTFE dispersion. The mixture was strained through a 70micrometer or finer filter to remove any large particles. The combinedsolution was then allowed to sit and/or mixed in a non-agitating jarroller until the solution achieved homogeneity; in some instances thatprocess takes 24 to 48 hours.

The combined solution was then rotational spun from a spinneret at about4500 RPM and collected on a 0.5 inch diameter rotating mandrel. Themandrel was rotated at about 200 RPM during this example. The mandrelwas positioned about 9.5 inches from the spinneret. The orifices on thespinneret were about 30 gauge openings. The mat was then sintered atabout 385 degrees C. for about 10 minutes.

It was observed that the fibers of the mat obtained in this example weregenerally aligned. The resultant mat was about 50 micrometers thick. Itwas further observed that the mat was generally less open. Similarly,the fiber diameters observed were generally of medium diameter.

FIG. 13A is an SEM of the rotational spun PTFE mat created in theprocedure of Example 3. As with FIG. 12A, FIG. 13A reflects amagnification of 170×. FIG. 13A illustrates the generally more aligneddispositions of fibers collected on a rotating mandrel. In particular,comparison of FIGS. 12A and 13A illustrates the effect of the use of arotating mandrel as opposed to a sheet collector, with respect to fiberalignment. FIG. 13B is an SEM of the rotational spun PTFE of FIG. 13A ata magnification of 950×.

Example 4

A 60 wt % PTFE water dispersion was mixed with PEO and water as follows.Water was added to PEO to maintain a ratio of 2.86 ml of water per gramof PEO. The water and PEO were mixed until the PEO was fully dissolvedand the solution created a thick gel. 21.43 ml of 60 wt % PTFE aqueousdispersion was added to the dissolved PEO to obtain a 0.10 g/ml mixtureof PEO to PTFE dispersion. The mixture was strained through a 70micrometer or finer filter to remove any large particles. The combinedsolution was then allowed to sit and/or mixed in a non-agitating jarroller until the solution achieved homogeneity; in some instances thatprocess takes 24 to 48 hours.

The combined solution was then rotational spun from a spinneret at about6000 RPM and collected on a 0.5 inch diameter rotating mandrel. Themandrel was rotated at about 200 RPM during this example. The mandrelwas positioned about 9.5 inches from the spinneret. The orifices on thespinneret were about 30 gauge openings. The mat was then sintered atabout 385 degrees C. for about 10 minutes.

It was observed that the fibers of the mat obtained in this example weregenerally aligned. The resultant mat was about 50 micrometers thick. Itwas further observed that the mat was generally open. Similarly, thefiber diameters observed were generally of large diameter.

FIG. 14A is an SEM of the rotational spun PTFE mat created in theprocedure of Example 4. FIG. 14A reflects a magnification of 170×. FIG.14B is an SEM of the rotational spun PTFE of FIG. 14A at a magnificationof 950×.

Example 5

A 60 wt % PTFE water dispersion was mixed with PEO and water as follows.Water was added to PEO to maintain a ratio of 2.86 ml of water per gramof PEO. The water and PEO were mixed until the PEO was fully dissolvedand the solution created a thick gel. 20.56 ml of 60 wt % PTFE aqueousdispersion was added to the dissolved PEO to obtain a 0.11 g/ml mixtureof PEO to PTFE dispersion. The mixture was strained through a 70micrometer or finer filter to remove any large particles. The combinedsolution was then allowed to sit and/or mixed in a non-agitating jarroller until the solution achieved homogeneity; in some instances thatprocess takes 24 to 48 hours.

The combined solution was then rotational spun from a spinneret at about8000 RPM and collected on a 2 inch by 2 inch sheet of aluminum foil. Thecollection sheet was positioned about 9.5 inches from the spinneret. Theorifices on the spinneret were about 30 gauge openings. The mat was thensintered at about 385 degrees C. for about 10 minutes.

It was observed that the mat created in this example had a largedistribution of fiber diameters, including some very large fibers. Theresultant mat was about 50 micrometers thick. It was further observedthat the mat was generally open. Similarly, the fiber diameters observedwere generally of large diameter.

FIG. 15 is an SEM of the rotational spun PTFE mat created in theprocedure of Example 5. FIG. 15 reflects a magnification of 950×.

Example 6

A 60 wt % PTFE water dispersion was mixed with PEO and water as follows.Water was added to PEO to maintain a ratio of 2.86 ml of water per gramof PEO. The water and PEO were mixed until the PEO was fully dissolvedand the solution created a thick gel. 21.43 ml of 60 wt % PTFE aqueousdispersion was added to the dissolved PEO to obtain a 0.10 g/ml mixtureof PEO to PTFE dispersion. The mixture was strained through a 70micrometer or finer filter to remove any large particles. The combinedsolution was then allowed to sit and/or mixed in a non-agitating jarroller until the solution achieved homogeneity; in some instances thatprocess takes 24 to 48 hours.

The combined solution was then rotational spun from a spinneret at about6000 RPM and collected on a 2 inch by 2 inch sheet of aluminum foil. Thecollection sheet was positioned about 9.5 inches from the spinneret. Theorifices on the spinneret were about 30 gauge openings. The mat was thensintered at about 385 degrees C. for about 10 minutes.

No beading was observed on the fibers of this mat. The resultant mat wasabout 50 micrometers thick. It was further observed that the mat wasgenerally less open. Similarly, the fiber diameters observed weregenerally of medium diameter.

FIG. 16A is an SEM of the rotational spun PTFE mat created in theprocedure of Example 6. FIG. 16A reflects a magnification of 170×. FIG.16B is an SEM of the rotational spun PTFE of FIG. 16A at a magnificationof 950×.

Example 7

A 60 wt % PTFE water dispersion was mixed with PEO and water as follows.Water was added to PEO to maintain a ratio of 2.86 ml of water per gramof PEO. The water and PEO were mixed until the PEO was fully dissolvedand the solution created a thick gel. 25.71 ml of 60 wt % PTFE aqueousdispersion was added to the dissolved PEO to obtain a 0.05 g/ml mixtureof PEO to PTFE dispersion. The mixture was strained through a 70micrometer or finer filter to remove any large particles. The combinedsolution was then allowed to sit and/or mixed in a non-agitating jarroller until the solution achieved homogeneity; in some instances thatprocess takes 24 to 48 hours.

The combined solution was then rotational spun from a spinneret at about3000 RPM and collected on a 2 inch by 2 inch sheet of aluminum foil. Thecollection sheet was positioned about 10 inches from the spinneret. Theorifices on the spinneret were about 30 gauge openings. The mat was thensintered at about 385 degrees C. for about 10 minutes.

This example produced the smallest diameter fibers of the examplesherein disclosed. The resultant mat was about 50 micrometers thick. Itwas further observed that the mat was generally closed. Again, the fiberdiameters observed were generally of small diameter.

FIG. 17A is an SEM of the rotational spun PTFE mat created in theprocedure of Example 7. FIG. 17A reflects a magnification of 170×. FIG.17B is an SEM of the rotational spun PTFE of FIG. 17A at a magnificationof 950×.

Example 8

A 60 wt % PTFE water dispersion was mixed with PEO and water as follows.Water was added to PEO to maintain a ratio of 2.86 ml of water per gramof PEO. The water and PEO were mixed until the PEO was fully dissolvedand the solution created a thick gel. 24.00 ml of 60 wt % PTFE aqueousdispersion was added to the dissolved PEO to obtain a 0.07 g/ml mixtureof PEO to PTFE dispersion. The mixture was strained through a 70micrometer or finer filter to remove any large particles. The combinedsolution was then allowed to sit and/or mixed in a non-agitating jarroller until the solution achieved homogeneity; in some instances thatprocess takes 24 to 48 hours.

The combined solution was then rotational spun from a spinneret at about3500 RPM and collected on a 0.5 inch diameter rotating mandrel. Themandrel was rotated at about 200 RPM during this example. The mandrelwas positioned horizontally in this example. The mandrel was positionedbetween about 4 inches and about 6 inches away from the spinneret, alongthe length of the mandrel. The orifices on the spinneret were about 30gauge openings. The mat was then sintered at about 385 degrees C. forabout 10 minutes.

The resultant mat was about 45 micrometers thick. It was furtherobserved that the mat was generally closed. Similarly, the fiberdiameters observed were generally of medium diameter.

FIG. 18A is an SEM of the rotational spun PTFE mat created in theprocedure of Example 8. FIG. 18A reflects a magnification of 170×. FIG.18B is an SEM of the rotational spun PTFE of FIG. 18A at a magnificationof 950×.

Example 9

Two separate nanofiber tubes were produced on a horizontal rotatingmandrel and each tube removed from the mandrel. Each tube was producedaccording to the same procedure recited in Example 8. The first of thetwo tubes was then placed on a 0.5 inch diameter mandrel and a solid,0.001 inch thick FEP film was wrapped one time around the first tube andmandrel. The FEP film was tacked in place with a soldering iron at about320 degrees C.

The second nanofiber tube was then pulled over the FEP film layer andthe entire construct placed in an oven for about 21 minutes at about 330degrees C. The construct was removed from the oven and allowed to cool,and the construct removed from the mandrel.

FIG. 19 is a cross sectional view of this layered construct at amagnification of 370×. As shown in this figure, the top and bottomlayers comprise nanofiber mats, while the middle FEP layer may beconfigured to be more impervious to tissue ingrowth and/or attachment.

Example 10

A 0.07 g/ml mixture of PEO to PTFE dispersion was rotational spun from aspinneret at about 3500 RPM and collected on a rotating mandrel. Themandrel was rotated at about 200 RPM and was positioned horizontally inthis example. The mandrel was positioned between about 4 inches andabout 6 inches away from the spinneret, along the length of the mandrel.The orifices on the spinneret were about 30 gauge openings. The mat wasthen sintered at about 385 degrees C. for about 10 minutes.

An FEP film was then placed around the mat and mandrel and an overwrapmaterial applied to compress the construct. The construct was thenheated to about 330 degrees C. for about 21 minutes. The FEP partiallymelted and flowed into the gaps or open spaces in the initially formedmat. The compression wrap was then removed.

FIG. 20 is an SEM of the PTFE/FEP construct at a magnification of 950×.The disposition and interaction of the FEP with respect to the PTFE canbe seen.

Example 11 Endothelial Cell Attachment Assay

In some embodiments, the degree of endothelial cell attachment to amaterial may be determined according to the following assay. As usedherein, values for “in vitro endothelial cell attachment” are determinedby following the procedure disclosed below.

In this assay, rotational spun PTFE sample materials were tested todetermine their ability to support the growth and/or attachment ofporcine aortic endothelial cells. One set of sample materials wasobtained from one of the rotational spun PTFE nanofiber mats describedin the preceding Examples. Further, materials A-I, described in Example14, infra, were also analyzed.

First, a standard curve with a range of endothelial cell seedingdensities was generated to correlate with the PTFE material samples. Togenerate this curve, a 96 well plate was prepared with duplicate sets of0, 2.5K, 5K, 10K, 20K, 40K, 60K, and 80K endothelial cells per well incomplete media. The endothelial cells were allowed to attach to the wellfor 90 minutes at 37° C. in 5% CO₂. At 90 minutes, 50 μl of a workingstock of 1 mg/ml XTT(2,3-Bis-(2-Methoxy-4-Nitro-5-Sulfophenyl)-2H-Tetrazolium-5-Carboxanilide)and 32 μM PMS (5-Methylphenazinium methyl sulfate) was added to eachwell and incubated at 37° C. in 5% CO₂ for 3 hours. Actively respiringcells convert the water-soluble XTT, in the presence of intermediateelectron acceptor PMS, to a water-soluble, orange formazan product.Thus, after the incubation period, formazan is in solution in the mediain each well. Following incubation, the media in each well was uniformlymixed by pipetting and 150 μl was transferred to wells in a new 96 wellplate. Once media from the standards and unknowns (described later) weretransferred to this plate, the optical density (OD) of each well wasread at 450 nm and at 650 nm. The background absorbance at 650 nm, wassubtracted from the 450 nm absorbance and the results were graphed.

As used herein, “optical density” measures the absorbance of light inthe solution. In this example, the greater the number of cells whichattach to the material, and are available to react with the XTT/PMS, thedarker the color of the supernatant (due to an increased amount offormazan) and, therefore, the higher the optical density (or absorbanceof light) of the sample. Assuming that all the cells in the experimentconvert XTT to its formazan derivative at the same rate, the opticaldensity measurement is directly proportional to the number of attachedcells.

To quantify the measurements obtained for the test materials, a standardcurve was generated by measuring the optical density using the wellsknown to contain 0, 2.5K, 5K, 10K, 20K, 40K, 60K, and 80K endothelialcells per well. The porcine aortic endothelial cells were cultured onthe rotational spun PTFE material samples to measure attachment ofendothelial cells to the material samples. In addition to the rotationalspun samples, a number of expanded PTFE (ePTFE) material samples werealso tested to provide a reference or comparison for the rotational spunmaterials. The ePTFE material used was the commercially available BardImpra Straight Thinwall Vascular Graft (Cat #80S06TW), which is oftenused as a control material in relevant literature as it is known to havea favorable biologic response and favorable endothelial cell attachment.

First the PTFE material samples to be tested and a number of Beemcapsules were ETO sterilized. The PTFE material samples were placedwithin the Beem capsules in an aseptic field. The PTFE materials werepre-wet with 200 μl of D-PBS (Dulbecco's phosphate buffered saline) for50 minutes. The D-PBS was removed from the Beem capsules containing thePTFE material samples and the Beem capsules were then seeded with 50Kendothelial cells in 200 μl of complete media, with the exception of aBeem control capsule which contained complete media only. The media-onlyBeem capsule control for each test material was processed identically asthe Beem capsules seeded with endothelial cells. A standard curve ofporcine endothelial cells (previously described) was seeded for eachunique assay of test materials.

The endothelial cells were allowed to attach 90 minutes at 37° C. in 5%CO₂. At 90 minutes, the Beem capsules were rinsed to remove unattachedcells. First the media was carefully removed and discarded. The Beemcapsules were then carefully rinsed with 200 μl D-PBS, which was removedand discarded. The Beem capsules then received 200 μl fresh media. 50 μlof working stock of 1 mg/ml XTT(2,3-Bis-(2-Methoxy-4-Nitro-5-Sulfophenyl)-2H-Tetrazolium-5-Carboxanilide)and 32 μM PMS (5-Methylphenazinium methyl sulfate) was added to eachBeem capsule and incubated at 37° C. in 5% CO₂ for 3 hours. As with thestandard curve wells outlined above, the XTT formazan was produced inproportion to the number of attached, live cells within each capsule.The media in each Beem capsule was uniformly mixed by pipetting and 150μl was transferred to an empty well in the clean 96 well platecontaining the supernatants of the standard curve series.

The optical density (OD) of the supernatants was read at 450 nm and 650nm. The background absorbance at 650 nm, was subtracted from the 450 nmabsorbance and the results were graphed. The number of cells attached toeach sample was interpolated from the standard curve results.

The number of cells attached to the rotational spun materials werecompared by normalizing the results to the number of cells attached theePTFE control material. The endothelial cell attachment for all of the10 rotational spun material samples (materials A-I from example 14 andone material from the preceding examples) was between 38.9% and 170%(about 40% to about 170%) of the endothelial cell attachment to theePTFE control material. Nine of the 10 materials had endothelial cellattachments above 50%; eight of the 10 were above 60%; seven of the 10were above 70%; five of the 10 were above 80%; four of the ten wereabove 100%; three of the ten were above 125%; and two of the 10 wereabove 150% of the endothelial cell attachment of the ePTFE controlmaterial.

The materials disclosed herein may be configured to achieve variousamounts of in vitro endothelial cell attachment as defined by thisassay. As described above, changes to the percent porosity of a mat, thethickness of the mat, and/or the diameter of fibers comprising the matmay influence the characteristics of the mat, including the response ofthe material to this assay. Thus, materials within the scope of thisdisclosure may have in vitro endothelial cell attachments of more than30%, more than 40%, more than 50%, more than 75%, more than 100%, morethan 125%, more than 150%, and more than 170% of the endothelial cellattachment of an ePTFE control material.

Example 12 Variations in RPM

A 0.08 g/ml mixture of PEO to PTFE dispersion was rotational spun from aspinneret at various rotational speeds from about 4500 RPM to about 7000RPM. The fibers were collected on a flat sheet then sintered at about385 degrees C. for about 15 minutes. FIGS. 21A-21E are SEMs of five matsproduced at different rotational speeds. FIG. 21A (170×) is an SEM of arotational spun material spun at 4500 RPM. FIG. 21B (170×) is an SEM ofa rotational spun material spun at 5000 RPM. FIG. 21C (170×) is an SEMof a rotational spun material spun at 5500 RPM. FIG. 21D (170×) is anSEM of a rotational spun material spun at 6000 RPM. FIG. 21E (170×) isan SEM of a rotational spun material spun at 7000 RPM.

It was observed during this and related experiments that the optimalrotational speed for a dispersion depended at least partially on otherparameters, such as the viscosity of the solution. In some embodiments,it was observed that particularly high or particularly low rotationalspeeds results in mats with particularly large fiber diameters, spray,broken fibers, or cracks. A variety of rotational speeds may beutilized, depending on, for example, the type of material to be spun andthe viscosity or other parameters of a particular solution. In someembodiments wherein a PEO/PTFE mixture is spun from a dispersion,rotational speeds may vary between about 1000 RPM and about 10,000 RPM,including rotational speeds from about 3000 RPM to about 5500 RPM.

Example 13 Variations in PEO/PTFE Concentration

As discussed in connection with Example 12, the viscosity of adispersion or mixture to be spun may affect fiber and mat formation. Inthis example, various concentrations of PEO to PTFE dispersion wererotational spun at 5000 RPM. The fibers were collected on a flat sheetthen sintered at about 385 degrees C. for about 15 minutes. FIGS.22A-22D are SEMs of four mats produced by spinning four differentconcentrations. FIG. 22A (170×) is an SEM of a rotational spun materialspun from a 0.08 g/ml PEO/PTFE mixture. FIG. 22B (170×) is an SEM of arotational spun material spun from a 0.09 g/ml PEO/PTFE mixture. FIG.22C (170×) is an SEM of a rotational spun material spun from a 0.10 g/mlPEO/PTFE mixture. FIG. 22D (170×) is an SEM of a rotational spunmaterial spun from a 0.11 g/ml PEO/PTFE mixture.

The mixtures having higher concentrations of PEO to PTFE dispersiontended to be more viscous than lower concentrations. Again, it wasobserved that the viscosity of the mixture and the concentration of PEOaffected the formation and deposition of fibers on the collector. Avariety of mixtures and viscosities may be utilized, depending on, forexample, the type of material to be spun and other parameters of theparticular solution. In some embodiments wherein a PEO/PTFE mixture isspun from a dispersion, concentrations of PEO to PTFE dispersion mayrange from about 0.08 g/ml to about 0.11 g/ml.

Example 14 In Vivo Biologic Response

Nine rotational spun PTFE mats, labeled materials A-I below, and threemultilayered constructs, labeled materials J, K, and L below, wereprepared to evaluate the relative biocompatibility of the materials invivo. Materials A-I were prepared by rotationally spinning a 0.06 g/mlPEO/PTFE mixture, collecting the fibers, and sintering the mats at 385degrees C. Various needle gauge sizes and rotational speeds were used tocreate the materials, as shown in Table 1 below. Each of materials A-Iwas measured to have a percent porosity between about 45% and about 50%.

TABLE 1 Needle Size Material (gauge) RPM A 32 7500 B 32 7500 C 32 7500 D30 4500 E 30 4500 F 27 3500 G 27 3500 H 27 3500 I 27 5500

The three multilayered constructs were prepared by rotationally spinninga 0.06 g/ml PEO/PTFE mixture using 30 gauge needles at 3500 RPM. Thefibers were collected and sintered at 385 degrees C. The PTFE mats werethen combined with additional film or dip layers as indicated in Table 2below. “RS Mat” in Table 2 indicates a rotational spun PTFE mat preparedas described in this paragraph.

TABLE 2 Material Layer 1 Layer 2 Layer 3 J RS Mat FEP Film RS Mat K RSMat FEP Dip RS Mat L RS Mat FEP/PTFE Dip RS Mat

In addition to materials A-L, two commercially available expanded PTFEstent graft materials, labeled ePTFE 1 and ePTFE 2 below, were alsoevaluated for comparison. Expanded PTFE (ePTFE) is a material producedby stretching a sheet or membrane of PTFE. Materials ePTFE 1 and ePTFE 2are used for implantation within the human body and are generallyunderstood to have favorable biocompatibility. Additionally, a portionof an expanded PTFE vascular graft material, labeled ePTFE Controlbelow, was also evaluated. This material is a commercially availableePTFE material produced by Bard which is often used as a positivecontrol material in relevant literature, as it generally exhibits afavorable biologic response. Finally, a polypropylene material, labeledPP Control, was evaluated as a negative control. PP Control was utilizedas a negative control as it is generally understood to elicit a moderateto high inflammatory biologic response.

Pledgets of materials A-L, ePTFE 1, ePTFE 2, ePTFE Control, and PPControl were cut or punched for subcutaneous implantation in murinemodels. Multiple samples of each material were prepared. The sampleswere ETO sterilized. The subjects were prepared for sterile surgicalprocedures. Each subject was ear tagged for unique study identificationand the ability to evaluate subjects based on subject number to maintainan investigator-blinded analysis of the data, prior to decoding thedata.

Each animal used in the study was randomly enrolled and received between4 and 5 subcutaneous implants; all implants in a single subject were ofthe same type of material facing the same direction. Documentation ofeach animal and the type of materials implanted were recorded onindividual animal surgery forms.

Following two weeks of implantation, all subjects were euthanized andthen implanted materials and surrounding tissue were explanted. Explantswere immediately placed into 2% paraformaldehyde fixative for up to 48hours and then changed into a 70% ethanol solution for subsequentprocessing for paraffin embedding. Prior to paraffin embedding, eachsample was cut in half and mounted into paraffin with the fresh cut sidedown. Samples processed for histology and immunohistochemistry werestained with hematoxlyin and eosin or trichrome, or reacted withantibodies for CD-68 (a marker for activated macrophages).

A. Inflammatory Score

The inflammatory response to the various implanted materials wascompared. To quantify the inflammatory response, an established equationwas used to provide weight to staining intensities and provide aquantitative value to the macrophage and foreign body gain cell (FBGC)counts. The equation was based on equations currently used bypathologists in cancer research called the H-score (Nakopoulou et al.,Human Pathology vol. 30, no. 4, April 1999). The H-score was obtained bythe formula:

(3×percentage of strongly staining nuclei)+(2×percentage of moderatelystaining nuclei)+(percentage of weakly staining nuclei)=a range of 0 to300

The inflammatory score obtained by this formula can be further indexedusing a qualitative approach considering the following criteria(Nakoploulou et al., 1999):

0=negative [0 to 50], 1=mild reactivity [51 to 100], 2=moderate [101 to200], 3=strong reactivity [201 to 300]

Strongly staining nuclei were represented by red in a false colormark-up in a digital algorithm, moderately stained nuclei wererepresented by orange in the false color mark-up, and weakly stainednuclei were represented by yellow. FIG. 24 is a color image of a stainedslide for one sample, within the original stained slide on the left, andthe digitally enhanced mark-up of the same image on the right. In themarked-up slide, red, orange, and yellow represent the staining leveldescribed above, while blue is negative. The black bar on the image is a100 μm scale bar. Similar slides for each sample were analyzed. Byinserting the counts from the marked up slides into the formula above, aquantitative inflammatory response was obtained for each sample. Theinflammatory score for each material was calculated as the average ofthe scores of each sample of the same material. A one-way ANOVA analysiswith a Tukey post-hoc test (p<0.05) was used to assess statisticaldifferences.

All of the 12 materials, A-L described above, were measured to have aninflammatory H-score under 100, meaning all 12 materials were eithermildly reactive or not reactive at all. 10 of the 12 materials weremeasured to have an inflammatory H-score under 90, seven to have aninflammatory H-score under 70, five to have an inflammatory H-scoreunder 55, three to have an inflammatory H-score under 50, and two tohave an inflammatory H-score under 40.

By comparison, materials ePTFE 1 and ePTFE had average inflammatoryH-scores of about 67 and about 85, respectively. The ePTFE Controlmaterial had an average inflammatory H-score of about 52 and the PPControl had an average inflammatory H-score of about 153. Thus, bycomparison, materials A-L exhibited inflammatory H-scores which werecomparable to, or more favorable than, the comparative materialsgenerally understood to have favorable biologic responses. Further, eachof the materials A-L exhibited a lower inflammatory H-score than themore reactive PP Control.

B. Fibrous Capsule Evaluation

The presence of a fibrous capsule on each sample was evaluated frommeasurements performed approximately 100 μm from the ends of each sampleand then every 100 μm across the superficial surface of each sample. Theaverage fibrous capsule for each type of material was determined byaveraging the measurements obtained from each sample of each type ofmaterial. FIG. 25 is an exemplary color image of a trichrome-stainedhistology light microscopy image for one sample. The width of thefibrous capsule, measured at two points in the image, is shown marked upon the image. Further a 100 μm scale bar is shown on the image. Similarimages were analyzed for each sample. A one-way ANOVA analysis with aTukey post-hoc test (p<0.05) was used to assess statistical differences.

All of the 12 materials, A-L described above, were measured to have anaverage fibrous capsule thickness of less than 35 μm, with 10 of 12having an average thickness of less than 30 μm, nine having an averagethickness of less than 25 μm, five having an average thickness of lessthan 20 μm, and three having an average thickness of less than 15 μm.

By comparison, materials ePTFE 1 and ePTFE had average fibrous capsulethicknesses of about 31 μm and about 20 μm, respectively. The ePTFEControl material had an average fibrous capsule thickness of about 22 μmand the PP Control had an average fibrous capsule thickness of about 20μm. As with the inflammatory H-score, it was noted that materials A-Lexhibited average fibrous capsule thicknesses which were similar to, ormore favorable than, the comparative materials generally known to havegood biocompatibility.

C. Cellular Penetration

Cellular penetration as a percentage of material thickness wasdetermined by performing measurements of the material thickness at 100μm intervals across each sample, as well as measuring the depth ofcellular penetration from the superficial surface toward the midline.The percent of cellular penetration was only measured on the superficialside of the samples. FIG. 26 is color image of a trichrome-stainedhistology light microscopy image for one sample of material J, a threelayered construct comprising a film FEP layer between two layers ofrotational spun PTFE. The dotted red lines marked up on the imageindicate the boundaries of the FEP layer, with the rotational spun PTFElayers on either side. The double black arrow indicates the relativedistance of cellular penetration and the positive stain indicates thepresence of cells within the material. Similar slides were analyzed foreach sample, and the results averaged for each material. A one-way ANOVAanalysis with a Tukey post-hoc test (p<0.05) was used to assessstatistical differences.

Of the nine single layer materials, A-I, described above, eight weremeasured to have an average cellular penetration of above 98%, with sixaveraging 99.99% or above. One of the nine materials, A-I, had anaverage cellular penetration of about 64%. By comparison, materialsePTFE 1 and ePTFE had an average cellular penetration of about 23% andabout 33%, respectively. The ePTFE Control material had an averagecellular penetration of about 23% and the PP Control had an averagecellular penetration of zero, meaning the material was substantiallyimpervious to cellular ingrowth. Thus, all nine of the single layermaterials, A-I, were found to exhibit greater cellular penetration thanthe comparative materials generally known to have good biocompatibility.Furthermore, the difference in cellular penetration between each ofmaterials A-I and any of ePTFE 1, ePTFE 2, the ePTFE Control, and the PPControl were shown to be statistically significant.

Materials J-L were multilayered constructs, meaning the total cellularpenetration may be impacted by the presence of multiple layers. In someinstances it may be desirable to construct a stent having certain layersconfigured to permit cellular penetration and certain layers configuredto resist cellular penetration. For example, a stent may comprise innerand outer layers configured to permit cellular ingrowth with a mid-layerconfigured to resist such ingrowth. The outer and inner layers may beconfigured to increase the biocompatability of the construct while themid-layer resists growth completely through the construct (which maylead to restenosis). The slide of FIG. 26 illustrates one suchembodiment, having permeable outer layers and a mid-layer configured toresist ingrowth. As shown in FIG. 26, the slide indicates essentially100 percent cellular penetration in the rotational spun outer layers, asshown by the presence of stained cells in this material. On the otherhand, the FEP layer, indicated by the dashed red lines, showssubstantially no cellular penetration. The dipped constructionsexhibited a similar response, with the dipped layers showingsubstantially no cellular penetration.

Exemplary Embodiments

The following embodiments are illustrative and exemplary and not meantas a limitation of the scope of the present disclosure in any way.

I. Medical Appliance

In one embodiment a medical appliance comprises a first layer ofrotational spun polytetrafluoroethylene (PTFE).

The rotational spun PTFE may comprise a mat of PTFE nanofibers.

The rotational spun PTFE may comprise a mat of PTFE microfibers.

The rotational spun PTFE may be rotational spun through an orifice.

The medical appliance may further comprise a second layer of rotationalspun PTFE fibers, wherein the first layer of rotational spun PTFE isdisposed such that it defines a first surface of the medical applianceand the second layer of rotational spun PTFE is disposed such that itdefines a second surface of the medical appliance.

The first layer of rotational spun PTFE may have an average percentporosity between about 30% and about 80%.

The first layer of rotational spun PTFE may have an average percentporosity of between about 40% and about 60%.

The first layer of rotational spun PTFE may have an average pore sizeconfigured to permit tissue ingrowth on the first surface of the medicalappliance.

The first layer of rotational spun PTFE may permit tissue ingrowth.

The second layer of rotational spun PTFE may have an average percentporosity of about 50% or less.

The second layer of rotational spun PTFE may have an average pore sizeconfigured to resist tissue ingrowth into or through the second surfaceof the medical appliance.

The medical appliance may further comprise a cuff adjacent to an end ofthe medical appliance, the cuff configured to permit tissue ingrowthinto or tissue attachment to the cuff.

A tie layer may be disposed between the first layer of rotational spunPTFE and the second layer of rotational spun PTFE.

The tie layer may be configured to inhibit tissue ingrowth into orthrough the tie layer.

The tie layer may be configured to inhibit fluid migration through thetie layer.

The first and second layers of rotational spun PTFE and the tie layermay be configured to inhibit an unfavorable inflammatory response.

The first and second layers of rotational spun PTFE and the tie layermay be configured to inhibit hyperplastic tissue growth includingneointimal or psuedointimal hyperplasia.

The tie layer may comprise PTFE.

The tie layer may be a thermoplastic polymer.

The tie layer may be a fluorinated ethylene propylene (FEP).

The FEP may partially bond to the fibers of the first and second layersof rotational spun PTFE.

The FEP may flow into and coat the fibers of the first and second layersof rotational spun PTFE.

The FEP may coat the fibers of the first and second layers whilemaintaining the porosity of the layers.

The rotational spun PTFE may be formed from a mixture comprising PTFE,polyethylene oxide (PEO), and water.

The mixture may be formed by combining a PTFE dispersion with PEOdissolved in water.

The PTFE may be rotational spun in the absence of an electric field.

The medical appliance may further comprise a main lumen extending to abifurcation and two branch lumens extending from the bifurcation.

The medical appliance may further comprise a main lumen and one or morebranch lumens extending from a wall of the main lumen.

The medical appliance may further comprising a reinforcing layer.

The reinforcing layer may comprise a tie layer.

The reinforcing layer may be comprised of expanded PTFE (ePTFE).

The ePTFE may be oriented to impart a particular property in aparticular direction.

The ePTFE may be oriented to resist creep in at least one direction.

The medical appliance may comprise multiple reinforcing layersconfigured to impart one or more properties in one or more directions.

II. Stent

In one embodiment, a stent comprises a frame configured to resist radialcompression when disposed in a lumen of a patient, and a coveringdisposed on at least a portion of the scaffolding structure, thecovering comprising a first layer of rotational spunpolytetrafluoroethylene (PTFE).

The rotational spun PTFE may comprise a mat of PTFE nanofibers.

The rotational spun PTFE may comprise a mat of PTFE microfibers.

The rotational spun PTFE may be rotational spun through an orifice.

The stent may further comprise a second layer of rotational spun PTFEfibers, wherein the stent is generally tubular in shape and the firstlayer of rotational spun PTFE is disposed such that it defines an insidesurface of the stent and the second layer of rotational spun PTFE isdisposed such that it defines an outside surface of the stent.

The first layer of rotational spun PTFE may have an average percentporosity between about 30% and about 80%.

The first layer of rotational spun PTFE may have an average percentporosity of between about 40% and about 60%.

The first layer of rotational spun PTFE may have an average pore sizeconfigured to permit the tissue ingrowth on the inside surface of thestent.

The first layer of rotational spun PTFE may permit tissue ingrowth.

The second layer of rotational spun PTFE may have an average percentporosity of about 50% or less.

The second layer of rotational spun PTFE may have an average pore sizeconfigured to resist tissue ingrowth into or through the second layer ofrotational spun PTFE.

The stent may further comprise a cuff adjacent to an end of the stent,the cuff configured to permit tissue ingrowth into the cuff.

A tie layer may be disposed between the first layer of rotational spunPTFE and the second layer of rotational spun PTFE.

The tie layer may be configured to inhibit tissue ingrowth into the tielayer.

The tie layer may be configured to inhibit fluid migration through thetie layer.

The tie layer may comprise PTFE.

The tie layer may be a thermoplastic polymer.

The tie layer may be fluorinated ethylene propylene (FEP).

The FEP may partially bond to the fibers of the first and second layersof rotational spun PTFE.

The second layer of rotational spun PTFE material may be configured topermit tissue ingrowth into the second layer to reduce device migration.

The first and second layers of rotational spun PTFE and the tie layermay be configured to inhibit hyperplastic tissue growth such asneointimal or psuedointimal hyperplasia.

The first and second layers of rotational spun PTFE and the tie layermay be configured to inhibit an unfavorable inflammatory response.

The FEP may flow into and coat the fibers of the first and second layersof rotational spun PTFE.

The FEP may coat the fibers of the first and second layers whilemaintaining the porosity of the layers.

The rotational spun PTFE may be formed from a mixture comprising PTFE,polyethylene oxide (PEO), and water.

The mixture may be formed by combining a PTFE dispersion with PEOdissolved in water.

The rotational spun PTFE may be rotational spun onto a rotating mandrel.

The PTFE may be rotational spun in the absence of an electric field.

The frame may be comprised of a single wire.

The wire may be helically wound around a central axis of the stent.

The wire may have a wave-like pattern defining apexes and arms.

Alternating apexes adjacent an end of the stent may have differentrelative heights.

Each apex may have a radius of between about 0.12 mm and 0.64 mm.

The stent may have a first portion disposed near the midbody of thestent and second and third portions disposed near the ends of the stent,and the arms disposed within the second and third portions may berelatively longer than the arms disposed within the first portion.

A distance, apex to apex length, may be defined as the distance betweena first apex and a second apex wherein the first apex lies on a firstcoil of wire and the second apex lies on a second coil of wire adjacentto the first coil, and wherein the first apex and the second apex liesubstantially on a line on the outer surface of the stent, the linebeing co-planar with and parallel to a central axis of the stent,wherein the apex to apex distance may be smaller at the midbody of thestent, relative to the apex to apex distance near the ends of the stent.

The stent may be structured such that a midbody portion of the stent isrelatively less compressible than a first and a second end of the stent.

The stent may further comprise a main lumen extending to a bifurcationand two branch lumens extending from the bifurcation.

The stent may further comprise a main lumen and one or more branchlumens extending from a wall of the main lumen.

The stent may further comprise a reinforcing layer.

The reinforcing layer may comprise a tie layer.

The reinforcing layer may be comprised of expanded PTFE (ePTFE).

The ePTFE may be oriented to impart a particular property in aparticular direction.

The ePTFE may be oriented to resist creep in at least one direction.

The stent may comprise multiple reinforcing layers configured to impartone or more properties in one or more directions.

III. Method of Constructing a Medical Appliance

In one embodiment, a method of constructing a medical appliancecomprises rotationally spinning a first tube of polytetrafluoroethylene(PTFE) onto a mandrel and sintering the first tube.

The first tube of PTFE may be rotational spun onto a rotating mandrel.

The mandrel may be positioned substantially orthogonal to an axis ofrotation of a rotational spinning spinneret.

A second tube of rotational spun PTFE may be applied around the firstlayer.

A scaffolding structure may be applied around the first tube and afluorinated ethylene propylene (FEP) layer may be applied around thefirst tube and the scaffolding structure, prior to applying the secondtube of rotational spun PTFE.

The FEP layer may be configured to inhibit tissue ingrowth into orthrough the FEP layer.

The medical appliance may be heated such that the FEP layer bonds to thefirst and second tubes.

The FEP may partially bond to the fibers of the first and second tubes.

The FEP may flow into and coat the fibers of the first and second tubes.

The FEP may coat the fiber of the first and second tubes whilemaintaining the porosity of the tubes.

The second tube of rotational spun PTFE may be formed by rotationalspinning the second tube of PTFE onto a rotating mandrel and sinteringthe second tube.

A compressive wrap may be applied around the second tube before themedical appliance is heat treated.

Rotational spinning the first tube of PTFE may comprise mixing a PTFEdispersion with polyethylene oxide (PEO), wherein the PEO is dissolvedin water to form a mixture, and discharging the mixture from an orificeonto a rotating mandrel.

The mixture may be discharged by centrifugal force.

A cuff may be coupled to an end of the medical appliance, the cuffconfigured to permit tissue ingrowth into the cuff.

The PTFE may be rotational spun in the absence of an electric field.

The mandrel may comprise a main portion and two leg portions, the mainportion configured to coincide with a main lumen of a bifurcated medicalappliance and the two leg portions configured to coincide with legportions of bifurcated medical appliance.

The two leg portions of the mandrel may be removable from the mainportion of the mandrel.

The first tube may be rotational spun by rotating the mandrel about anaxis of the leg portions of the mandrel while rotationally spinningfibers and rotating the mandrel about an axis of the main portion of themandrel while rotationally spinning fibers.

IV. Method for Promoting Endothelial Cell Growth

In one embodiment, a method for promoting endothelial cell growth on aimplantable medical appliance comprises implanting the medical applianceinto a patient, the medical appliance coated with at least one spunfibrous polymer layer having a percent porosity of between about 30% andabout 80%, such that endothelial cells grow on or attach to the surfaceof the at least one polymer layer.

The implantable medical appliance may comprise a covered stent or astent graft.

The implantable medical appliance may comprise a graft.

The at least one fibrous polymer layer may comprise a fibrous PTFElayer.

The medical appliance may be coated with a second polymer layer thatinhibits ingrowth of tissue.

The second polymer layer may comprise an FEP layer.

The fibrous PTFE may comprise a fiber mat of rotationally-spunrandomized PTFE microfibers or nanofibers.

The at least one polymer layer of the implanted medical appliance may beconfigured to permit at least 50% in vitro endothelial cell attachment,compared to an ePTFE control material.

The at least one polymer layer of the implanted medical appliance may beconfigured to permit at least 75% in vitro endothelial cell attachment,compared to an ePTFE control material.

The at least one polymer layer of the implanted medical appliance may beconfigured to permit at least 100% in vitro endothelial cell attachment,compared to an ePTFE control material.

The at least one polymer layer of the implanted medical appliance may beconfigured to permit at least 125% in vitro endothelial cell attachment,compared to an ePTFE control material.

The at least one polymer layer of the implanted medical appliance may beconfigured to permit at least 150% in vitro endothelial cell attachment,compared to an ePTFE control material.

The percent porosity of the at least one polymer layer may be betweenabout 40% and about 60%.

In any of the above methods for promoting endothelial cell growth, thespun fibrous polymer layer may be configured to permit at least 50%,75%, 90%, 95%, or 100% cellular penetration, in vivo two weeks aftermurine implantation.

In any of the above methods for promoting endothelial cell growth, thespun fibrous polymer layer may be configured to inhibit a neointimalhyperplasia response.

In any of the above methods for promoting endothelial cell growth, thespun fibrous polymer layer, when placed in vivo, may have an H-score ofless than 100, 90, 70, or 50 two weeks after murine implantation.

In any of the above methods for promoting endothelial cell growth, thespun fibrous polymer layer, when placed in vivo, may be configured toresist fibrous capsule formation, such that the spun fibrous polymerlayer has an average fibrous capsule thickness of less than 35 μm, 30μm, 25 μm, 20 μm, or 15 μm two weeks after murine implantation.

V. Method for Promoting Cellular Growth into an Implantable MedicalAppliance

In one embodiment, a method for promoting cellular growth into animplantable medical appliance comprises obtaining a medical appliancecoated with at least one spun fibrous polymer layer and at least onelayer that is substantially impervious to cellular growth, andimplanting the medical appliance into a patient such that the fibrouspolymer layer of the medical appliance is in direct contact with bodyfluid or body tissue.

The at least one fibrous polymer layer may be configured to permit atleast 50% cellular penetration, in vivo two weeks after murineimplantation.

The at least one fibrous polymer layer may be configured to permit atleast 75% cellular penetration, in vivo two weeks after murineimplantation.

The at least one fibrous polymer layer may be configured to permit atleast 90% cellular penetration, in vivo two weeks after murineimplantation.

The at least one fibrous polymer layer may be configured to permit atleast 95% cellular penetration, in vivo two weeks after murineimplantation.

The at least one fibrous polymer layer may be configured to permitsubstantially 100% cellular penetration, in vivo two weeks after murineimplantation.

The at least one substantially impervious layer may be configured topermit less than 20% cellular penetration, in vivo two weeks aftermurine implantation.

The at least one substantially impervious layer may be configured topermit less than 10% cellular penetration, in vivo two weeks aftermurine implantation.

The at least one substantially impervious layer may be configured topermit substantially no cellular penetration, in vivo two weeks aftermurine implantation.

The at least one substantially impervious layer may be configured toinhibit fluid migration through the layer.

In any of the above methods for promoting endothelial cell growth on animplantable medical appliance, the at least one fibrous polymer layermay be configured to permit at least 50%, 75%, 100%, 125%, or 150% invitro endothelial cell attachment, compared to an ePTFE controlmaterial.

In any of the above methods for promoting endothelial cell growth on animplantable medical appliance, the at least one fibrous polymer layermay be configured to inhibit a neointimal hyperplasia response.

In any of the above methods for promoting endothelial cell growth on animplantable medical appliance, the at least one fibrous polymer layer,when placed in vivo, may have an H-score of less than 100, 90, 70, or 50two weeks after murine implantation.

In any of the above methods for promoting endothelial cell growth on animplantable medical appliance, the at least one fibrous polymer layer,when placed in vivo, may be configured to resist fibrous capsuleformation, such that the spun fibrous polymer layer has an averagefibrous capsule thickness of less than 35 μm, 30 μm, 25 μm, 20 μm, or 15μm two weeks after murine implantation.

VI. Method for Inhibiting a Neointimal Hyperplasia Response to anImplantable Medical Appliance

In one embodiment, a method for inhibiting a neointimal hyperplasiaresponse to an implantable medical appliance comprises implanting themedical appliance into a patient, the medical appliance coated with aspun fibrous polymer layer comprising a porous mat and a second polymerlayer that inhibits tissue ingrowth into or through the second polymerlayer.

The fibrous polymer layer may permit endothelial cell growth orattachment on the surface of the fibrous polymer layer.

The fibrous polymer layer may comprise a fibrous PTFE layer and thesecond polymer layer may comprise an FEP layer.

The medical appliance may be coated with a third polymer layercomprising a fibrous PTFE layer, such that the FEP layer is disposedbetween the fibrous polymer layer and the third polymer layer.

The fibrous polymer layer and the third polymer layer may each comprisea rotational spun micro or nano-fiber PTFE mat.

The second polymer layer may comprise a rotational spun FEP mat.

In any of the above methods for inhibiting a neointimal hyperplasiaresponse to an implantable medical appliance, the fibrous polymer layermay be configured to permit at least 50%, 75%, 100%, 125%, or 150% invitro endothelial cell attachment, compared to an ePTFE controlmaterial.

In any of the above methods for inhibiting a neointimal hyperplasiaresponse to an implantable medical appliance, the fibrous polymer layermay be configured to permit at least 50%, 75%, 90%, 95%, or 100%cellular penetration, in vivo two weeks after murine implantation.

In any of the above methods for inhibiting a neointimal hyperplasiaresponse to an implantable medical appliance, the fibrous polymer layer,when placed in vivo, may have an H-score of less than 100, 90, 70, or 50two weeks after murine implantation.

In any of the above methods for inhibiting a neointimal hyperplasiaresponse to an implantable medical appliance, the fibrous polymer layer,when placed in vivo, may be configured to resist fibrous capsuleformation, such that the fibrous polymer layer has an average fibrouscapsule thickness of less than 35 μm, 30 μm, 25 μm, 20 μm, or 15 μm twoweeks after murine implantation.

VII. Method for Inhibiting an Inflammatory Response to an ImplantableMedical Appliance

In one embodiment, a method for inhibiting an inflammatory response toan implantable medical appliance, comprises implanting the medicalappliance into a patient, the medical appliance coated with a spunfibrous polymer layer wherein the spun fibrous polymer layer, whenplaced in vivo, has an H-score of less than 100 two weeks after murineimplantation.

The spun fibrous polymer layer, when placed in vivo, may have an H-scoreof less than 90 two weeks after murine implantation.

The spun fibrous polymer layer, when placed in vivo, may have an H-scoreof less than 70 two weeks after murine implantation.

The spun fibrous polymer layer, when placed in vivo, may have an H-scoreof less than 50 two weeks after murine implantation.

The fibrous polymer layer may comprise a porous, rotational spun PTFEmat.

In any of the above methods for inhibiting an inflammatory response toan implantable medical appliance, the fibrous polymer layer may beconfigured to permit at least 50%, 75%, 100%, 125%, or 150% in vitroendothelial cell attachment, compared to an ePTFE control material.

In any of the above methods for inhibiting an inflammatory response toan implantable medical appliance, the fibrous polymer layer may beconfigured to permit at least 50%, 75%, 90%, 95%, or 100% cellularpenetration, in vivo two weeks after murine implantation.

In any of the above methods for inhibiting an inflammatory response toan implantable medical appliance, the fibrous polymer layer may beconfigured to inhibit a neointimal hyperplasia response.

In any of the above methods for inhibiting an inflammatory response toan implantable medical appliance, the fibrous polymer layer, when placedin vivo, may be configured to resist fibrous capsule formation, suchthat the fibrous polymer layer has an average fibrous capsule thicknessof less than 35 μm, 30 μm, 25 μm, 20 μm, or 15 μm two weeks after murineimplantation.

VIII. Method for Inhibiting Growth of a Fibrous Capsule on a MedicalAppliance

In one embodiment, a method for inhibiting growth of a fibrous capsuleon a medical appliance comprises implanting the medical appliance into apatient, the medical appliance coated with a spun fibrous polymer layer,wherein the fibrous polymer layer, when placed in vivo, is configured toresist fibrous capsule formation, such that the fibrous polymer layerhas an average fibrous capsule thickness of less than 35 μm two weeksafter murine implantation.

The fibrous polymer layer may have an average fibrous capsule thicknessof less than 30 μm two weeks after murine implantation.

The fibrous polymer layer may have an average fibrous capsule thicknessof less than 25 μm two weeks after murine implantation.

The fibrous polymer layer may have an average fibrous capsule thicknessof less than 20 μm two weeks after murine implantation.

The fibrous polymer layer may have an average fibrous capsule thicknessof less than 15 μm two weeks after murine implantation.

The fibrous polymer layer may comprise a porous, rotational spun PTFEmat.

In any of the above methods for method for inhibiting growth of afibrous capsule on a medical appliance, the fibrous polymer layer may beconfigured to permit at least 50%, 75%, 100%, 125%, or 150% in vitroendothelial cell attachment, compared to an ePTFE control material.

In any of the above methods for method for inhibiting growth of afibrous capsule on a medical appliance, the fibrous polymer layer may beconfigured to permit at least 50%, 75%, 90%, 95%, or 100% cellularpenetration, in vivo two weeks after murine implantation.

In any of the above methods for method for inhibiting growth of afibrous capsule on a medical appliance, the fibrous polymer layer may beconfigured to inhibit a neointimal hyperplasia response.

In any of the above methods for method for inhibiting growth of afibrous capsule on a medical appliance, the fibrous polymer layer, whenplaced in vivo, may have an H-score of less than 100, 90, 70, or 50 twoweeks after murine implantation.

While specific embodiments of stents and other medical appliances havebeen illustrated and described, it is to be understood that thedisclosure provided is not limited to the precise configuration andcomponents disclosed. Various modifications, changes, and variationsapparent to those of skill in the art having the benefit of thisdisclosure may be made in the arrangement, operation, and details of themethods and systems disclosed, with the aid of the present disclosure.

Without further elaboration, it is believed that one skilled in the artcan use the preceding description to utilize the present disclosure toits fullest extent. The examples and embodiments disclosed herein are tobe construed as merely illustrative and exemplary and not as alimitation of the scope of the present disclosure in any way. It will beapparent to those having skill in the art, and having the benefit ofthis disclosure, that changes may be made to the details of theabove-described embodiments without departing from the underlyingprinciples of the disclosure herein.

1. A medical appliance, comprising: a first layer of rotational spunpolytetrafluoroethylene (PTFE).
 2. The medical appliance of claim 1,wherein the rotational spun PTFE is rotational spun through an orifice.3. The medical appliance of claim 1, wherein the medical appliancefurther comprises a second layer of rotational spun PTFE, wherein thefirst layer of rotational spun PTFE is disposed such that it defines afirst surface of the medical appliance and the second layer ofrotational spun PTFE is disposed such that it defines a second surfaceof the medical appliance.
 4. The medical appliance of claim 3, whereinthe first layer of rotational spun PTFE has an average percent porositybetween about 30% and about 80%.
 5. The medical appliance of claim 3,wherein the first layer of rotational spun PTFE has an average pore sizeconfigured to permit tissue ingrowth on the first surface of the medicalappliance.
 6. The medical appliance of claim 5, wherein the second layerof rotational spun PTFE has an average percent porosity of about 50% orless.
 7. The medical appliance of claim 5, wherein the second layer ofrotational spun PTFE has an average pore size configured to resisttissue ingrowth into or through the second surface of the medicalappliance.
 8. The medical appliance of claim 5, wherein a tie layer isdisposed between the first layer of rotational spun PTFE and the secondlayer of rotational spun PTFE and wherein the tie layer is configured toinhibit tissue or fluid migration into or through the tie layer.
 9. Themedical appliance of claim 8, wherein the tie layer comprises PTFE. 10.The medical appliance of claim 8, wherein the tie layer is fluorinatedethylene propylene (FEP).
 11. The medical appliance of claim 10, whereinthe FEP partially bonds to the fibers of the first and second layers ofrotational spun PTFE.
 12. The medical appliance of claim 11, wherein theFEP flows into and coats the fibers of the first and second layers ofrotational spun PTFE while maintaining the porosity of the layers. 13.The medical appliance of claim 1, further comprising a reinforcing layercomprised of expanded PTFE, wherein the expanded PTFE is oriented toresist creep in at least one direction.
 14. A stent, comprising: a frameconfigured to resist radial compression when disposed in a lumen of apatient, and a covering disposed on at least a portion of the frame, thecovering comprising a first layer of rotational spunpolytetrafluoroethylene (PTFE).
 15. The stent of claim 14, wherein thestent further comprises a second layer of rotational spun PTFE, whereinthe stent is generally tubular in shape and the first layer ofrotational spun PTFE is disposed such that it defines an inside surfaceof the stent and the second layer of rotational spun PTFE is disposedsuch that it defines an outside surface of the stent.
 16. The stent ofclaim 15, wherein the first layer of rotational spun PTFE has an averagepercent porosity between about 30% and about 80%.
 17. The stent of claim15, wherein the first layer of rotational spun PTFE has an average poresize configured to permit the tissue ingrowth on the inside surface ofthe stent.
 18. The stent of claim 15, wherein the second layer ofrotational spun PTFE has an average percent porosity of about 50% orless.
 19. The stent of claim 15, wherein the second layer of rotationalspun PTFE has an average pore size configured to resist tissue ingrowthinto or through the second layer of rotational spun PTFE.
 20. The stentof claim 15, further comprising a cuff adjacent to an end of the stent,the cuff configured to permit tissue ingrowth into the cuff.
 21. Thestent of claim 15, wherein a tie layer is disposed between the firstlayer of rotational spun PTFE and the second layer of rotational spunPTFE and wherein the tie layer is configured to inhibit tissue or fluidmigration into or through the tie layer.
 22. The stent of claim 21,wherein the tie layer is fluorinated ethylene propylene (FEP).
 23. Thestent of claim 21, wherein the second layer of rotational spun PTFEmaterial is configured to permit tissue ingrowth into the second layerto reduce device migration.
 24. The stent of claim 15, wherein the frameis comprised of a single wire wound in a wave-like pattern such thatalternating apexes adjacent an end of the stent have different relativeheights.
 25. The stent of claim 15, further comprising a main lumenextending to a bifurcation and two branch lumens extending from thebifurcation.
 26. The stent of claim 15, further comprising a main lumenand one or more branch lumens extending from a wall of the main lumen.27. The stent of claim 14, wherein the cover further comprises areinforcing layer comprised of expanded PTFE, wherein the expanded PTFEis oriented to resist creep in at least one direction.
 28. A method ofconstructing a medical appliance, comprising: rotationally spinning afirst tube of polytetrafluoroethylene (PTFE) onto a mandrel andsintering the first tube.
 29. The method of claim 28, wherein the firsttube of PTFE is rotational spun onto a rotating mandrel.
 30. The methodof claim 29, wherein the mandrel is positioned substantially orthogonalto an axis of rotation of a rotational spinning spinneret.
 31. Themethod of claim 28, further comprising applying a second tube ofrotational spun PTFE around the first layer.
 32. The method of claim 31,further comprising: applying a scaffolding structure around the firsttube and applying a fluorinated ethylene propylene (FEP) layer aroundthe first tube and the scaffolding structure, prior to applying thesecond tube of rotational spun PTFE.
 33. The method of claim 32, furthercomprising heating the medical appliance such that the FEP layer bondsto the first and second tubes such that the FEP partially bonds to thefibers of the first and second tubes.
 34. The method of claim 33,wherein the FEP flows into and coats the fibers of the first and secondtubes while maintaining the porosity of the tubes.
 35. The method ofclaim 31, wherein the second tube of rotational spun PTFE is formed by amethod comprising: rotational spinning the second tube of PTFE onto arotating mandrel; and sintering the second tube.
 36. The method of claim33, further comprising applying a compressive wrap around the secondtube before the medical appliance is heat treated.
 37. The method ofclaim 28, wherein rotational spinning the first tube of PTFE comprises:mixing a PTFE dispersion with polyethylene oxide (PEO), wherein the PEOis dissolved in water to form a mixture; and discharging the mixturefrom an orifice onto the rotating mandrel.
 38. The method of claim 28,wherein the mandrel comprises a main portion and two leg portions, themain portion configured to coincide with a main lumen of a bifurcatedmedical appliance and the two leg portions configured to coincide withleg portions of bifurcated medical appliance.
 39. The method of claim38, wherein the two leg portions of the mandrel are removable from themain portion of the mandrel.
 40. The method of claim 38, wherein thefirst tube is rotational spun by rotating the mandrel about an axis ofthe leg portions of the mandrel while rotationally spinning fibers androtating the mandrel about an axis of the main portion of the mandrelwhile rotationally spinning fibers.